Prevalencia de lesiones en mucosa bucal y su relación con condición sistémica, edad y sexo / Prevalence of lesions in the oral mucosa and its relationship with systemic condition, age and gender

Este estudio tiene la finalidad de analizar la prevalencia de variantes de la normalidad y patología en la mucosa de la cavidad bucal por zona anatómica, de una población controlada en una clínica estomatológica universitaria de pregrado en el Estado de México. Se trata de un estudio transversal, descriptivo y observacional de 542 pacientes, de los cuales el 62.7% (340) pertenecen al sexo femenino y 37.3% (202) al masculino; la edad se distribuyó en un rango de dos a 85 años con una media de 28 años y fue categorizada en cinco grupos etarios: 2 a 12, 13 a 18, 19 a 35, 36 a 69 y > 70 años. En este estudio participaron una especialista en patología bucal, un especialista en odontopediatría y una pasante de la licenciatura de estomatología quien fungió como ayudante de investigación. Fueron identificadas 13 variantes de la normalidad y 52 lesiones en total, mismas que son reportadas por zona anatómica, por rangos de edad y por sexo. El número de condiciones y lesiones diagnosticadas por paciente varió de una a cinco en 87.27% y en el restante 12.73% no se detectó ninguna. Las variantes de la normalidad o condiciones más frecuentes fueron lengua fisurada con 12.17%, apéndice mucoso en frenillo vestibular con 11.25% y gránulos de Fordyce con 10.88%. Las lesiones más prevalentes por zona anatómica fueron: nevo intradérmico con 2.39% en labio externo superior e inferior; queilitis simple con 11.43% en la interfase de piel y mucosa de los labios (borde bermellón); úlcera traumática con 3.87% en mucosa labial; absceso de origen dental con 1.42 en encía; frenillo con inserción baja 1.84% en frenillos; úlcera traumática con 5.53% en mucosa bucal; candidiasis atrófica crónica con 5.53% en paladar; amígdalas hipertróficas con 8.11% en zona amigdalina; lengua pilosa con 1.66% en lengua; úlcera traumática con 3.69% en piso de boca; granuloma piógeno con 0.18% en proceso alveolar; y por último, hipertrofia de glándulas salivales labiales con 0.55% asociadas a presencia de aparatología ortodóntica. Finalmente se llevó a cabo una prueba de χ2 de Pearson para establecer correlación entre variables dependientes e independientes, encontrando significancia estadística de p < 0.000 entre lesiones de lengua y condición sistémica y edad en relación a lesiones de lengua, paladar y labios con p < 0.000 (AU)

The purpose of this study is to analyze the prevalence of variants of normality and pathology in the mucosa of the oral cavity by anatomical area in a controlled population in a university undergraduate stomatological clinic in the state of Mexico. This is a cross-sectional, descriptive and observational study of 542 patients, of which 62.7% (340) belonged to the female gender and 37.3% (202) to the male gender, the age was distributed in a range of two to 85 years with a mean of 28 years and was categorized in five age groups: 2 to 12, 13 to 18, 19 to 35, 36 to 69 and > 70 years. A specialist in oral pathology, a specialist in pediatric dentistry and an intern in stomatology who served as a research assistant participated in this study. Thirteen variants of normality and 52 lesions in total were identified and reported by anatomical area, age range and gender. The number of conditions and lesions diagnosed per patient ranged from one to five in 87.27% and none were detected in 12.73% of the population studied. The most frequent variants of normality or conditions were fissured tongue with 12.17%, mucous appendage in the vestibular frenulum with 11.25% and Fordyce granules with 10.88%. The most prevalent lesions by anatomical area were: intradermal nevus with 2.39% in upper and lower external lip; simple cheilitis with 11.43% in the interphase interface of skin and mucosa of the lips (vermilion border); traumatic ulcer with 3.87% in labial mucosa; abscess of dental origin with 1.42 in gingiva; frenulum with low insertion 1.84% in frenulum; traumatic ulcer with 5. 53% in buccal mucosa; chronic atrophic candidiasis with 5.53% in palate; hypertrophic tonsils with 8.11% in tonsillar area; hairy tongue with 1.66% in tongue; traumatic ulcer with 3.69% in floor of mouth; pyogenic granuloma with 0.18% in alveolar process and finally; hypertrophy of labial salivary glands with 0.55% associated with the presence of orthodontic appliances. Finally, a Pearson's χ2 test was carried out to establish correlation between dependent and independent variables, finding statistical significance of p < 0.000 between tongue lesions and systemic condition and age in relation to tongue, palate and lip lesions with a p < 0.000 (AU)

Efficacy and adverse reactions of donepezil:a pharmacogenomic study / 中华老年心脑血管病杂志

Objective To analyze the efficacy and adverse reactions of donepezil in the treatment of patients with a continuous disease spectrum of Alzheimer's disease(AD)with pharmacogenomics.Methods Seventy-two patients who took donepezil therapy at the time of initial molecular pa-thology diagnosis of AD continuous disease spectrum in Chinese PLA General Hospital from Jan-uary 2022 to January 2023 were recruited.Cells from the oral buccal mucosa were collected,and MassARRAY nucleic acid mass spectrometry was applied to detect the genotypes of CYP2D6,the gene encoding cytochrome P450 2D6 enzyme,and CHAT,the gene encoding acetylcholine trans-ferase.After 9 months of follow-up,drug efficacy was indirectly determined by neurological func-tion scales,caregiver evaluations,and drug prescribing behaviors,and thus,the 50 patients on donepezil alone were divide into effective group(n=28)and ineffective group(n=22).Seventy-two patients were divided into adverse reaction group(n=12)and no adverse reaction group(n=60).Multivariate logistic regression analysis was used to analyze the correlation between donepezil efficacy and pharmacogenomics.Results The frequencies of CHAT rs3793790 locus carrying G allele and rs2177370 locus carrying A allele were significantly higher in the effective group than the ineffective group(35.71％vs 9.09％,P=0.029;42.86％vs 9.09％,P=0.008).Multivariate lo-gistic regression analysis showed that donepezil was more effective in those who carrying rs3793790 G allele and/or rs2177370 A allele in the CHAT gene than those who carrying neither of the alleles(95％CI:1.20-34.47,P=0.030).There were no statistical differences in the CYP2D6 gene-adjusted activity score and whether or not carrying*10 between the patients with and without adverse reactions(P＞0.0 5).Conclusion In patients with a continuous spectrum of AD,donepezil efficacy is associated with CHAT gene polymorphisms,but there is no correlation between donepezil adverse reactions and CYP2D6 genotype.

Analysis of the clinical presentation and genetic profile of epilepsy-aphasia spectrum due to GRIN2A gene mutations / 中华神经科杂志

Objective:To explore the clinical phenotypic features and genetic variation characteristics of children with epilepsy-aphasia spectrum due to GRIN2A gene variants confirmed by second-generation sequencing. Methods:The clinical data of 5 children with epilepsy-aphasia spectrum with epileptic onset diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University, from February 2019 to November 2022 were retrospectively analyzed. Whole-exome genome sequencing of the probands using a second-generation sequencing method confirmed that all 5 cases were children with the GRIN2A gene variant. The characteristics of the GRIN2A gene variants were analyzed. Results:Among the 5 children diagnosed with epileptic aphasia spectrum due to GRIN2A gene variants, the male-to-female ratio was 4∶1, and the age range of onset was 1.5-4.4 years. The clinical phenotype included seizures in all cases, language and intellectual developmental deficits in 4 cases, and attention deficit hyperactivity disorder in 3 cases. The seizures were manifested as focal seizures or secondary generalized seizures, and were effectively controlled with antiepileptic drugs. Among the 5 children, gene variant of case 1 was originated from a paternal heterozygous variant, and cases 2-5 had de novo variants, which were c.2107C>T (p.Gln703 *) nonsense variant, c.2284G>A (p.Gly762Arg) missense variant, c.2197del (p.Ala733Glnfs *3) shifted coding variant, c.2511G>A (p.Trp837 *) nonsense variant, and c.1651+1G>C shear site variant, respectively. None of the 5 loci were reported in the literature. Conclusions:Epilepsy-aphasia spectrum is an epilepsy syndrome with a complex onset, and may have different phenotypes at different genetic variant loci, with focal seizures or secondary generalized seizures, which can be effectively controlled with anti-seizure medication. The GRIN2A gene variant is the genetic etiology of the epileptic aphasia spectrum.

Detection of germline variants in pancreatic cancer by next-generation sequencing and correlation analysis of clinical factors / 复旦学报（医学版）

Objective To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants.Methods A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study.Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing,and the relationship between germline variants and clinical factors such as age of onset,family history and personal history was analyzed.Results The rate of germline P/LP variants was 6.3%in unselected pancreatic cancer patients,but was high as 17.1%in genetic high-risk group patients(those with a family or personal history of cancer,or early-onset).Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2,BRCA2,and ATM.Conclusion The rate of germline variants in overall pancreatic cancer patients is not high,but it increases significantly in genetic high-risk group,proving the importance of clinical factors in the screening of hereditary pancreatic cancer.

Clinical application study on capillary electrophoresis-based gene diagnosis of hyperphenylalaninemia / 中华实用儿科临床杂志

Objective:To evaluate the clinical value of a capillary electrophoresis-based method for gene diagnosis of hyperphenylalaninemia.Methods:In this single-center prospective study, 40 newborns with suspected hyperphenylalaninemia detected by neonatal liquid chromatography-tandem mass spectrometry screening at Nanjing Maternity and Child Health Care Hospital from February 2021 to February 2023 were included, with 22 males, 18 females and a mean age at diagnosis of 21.93 days.Capillary electrophoresis was used to detect 85 variants of the phenylalanine hydroxylase ( PAH) gene in 40 newborns with suspected hyperphenylalaninemia.The PAH gene of undiagnosed patients was further analyzed by Sanger sequencing.The detection rate, sensitivity and specificity of capillary electrophoresis were calculated. Results:Among these 40 newborns with suspected hyperphenylalaninemia, 71 PAH variants were detected by capillary electrophoresis, 32 patients were clearly diagnosed, only 1 pathogenic variant was found in 5 patients, and no pathogenic variant was found in the last 3 patients.Therefore, the detection rate, sensitivity and specificity of capillary electrophoresis for analysis of the PAH gene were 80.00%, 88.75% and 100%, respectively. Conclusions:The capillary electrophoresis-based method can rapidly, efficiently and accurately detect PAH gene variants at lower cost and is a promising gene detection method for hyperphenylalaninemia in clinical practice.

Novas variantes de KPC em isolados do Complexo Klebsiella pneumoniae resistentes à ceftazidima-avibactam / New KPC variants in ceftazidime-avibactam-resistant K. pneumoniae Complex isolates

O Complexo K. pneumoniae (C-Kp) é o principal grupo de bacilos Gram-negativos responsáveis por infecções nosocomiais graves em todo o mundo e o tratamento empírico dessas infecções usualmente inclui os carbapenêmicos. O principal mecanismo de resistência a essa classe de antimicrobianos é a expressão de carbapenemases, e no Brasil, mais frequentemente as do tipo KPC. Em março de 2019 a ceftazidima-avibactam foi disponibilizada para uso clínico no Brasil, sendo amplamente utilizada no tratamento infecções causadas por bacilos gram-negativos produtores de KPC. Diversos países já relataram a presença de K. pneumoniae produtores de KPC resistentes à ceftazidima-avibactam. No entanto, há poucos relatos dessa ocorrência no Brasil. O objetivo deste trabalho foi caracterizar genotipicamente e fenotipicamente isolados do C-Kp produtores de KPC, resistentes à ceftazidima-avibactam. No período de julho/2019 a julho/2021, 46 isolados do C-Kp, um por paciente, foram detectados em diferentes sítios de infecção ou culturas de vigilância de pacientes internados em hospitais privados de seis estados brasileiros. Os isolados tiveram seu genoma completo sequenciado nas plataformas MiSeq e MinION para determinação da variante alélica de blaKPC e avaliação do seu contexto genético. As taxas de resistência ao ertapenem e à ceftazidima-avibactam foram calculadas a partir de banco de dados. A clonalidade dos isolados foi avaliada por PFGE e MLST. A localização plasmidial do gene blaKPC foi confirmada por conjugação e/ou transformação. A concentração inibitória mínima (CIM) para betalactâmicos foi determinada por microdiluição em caldo segundo o BrCAST. Ensaios imunocromatográficos, NG-Test CARBA-5 e O.K.N.V.I. RESIST-5, foram avaliados quanto à sua performance na detecção de variantes KPC. A taxa de resistência ao ertapenem entre isolados do C-Kp aumentou 15,6% em 2019 para 27,3% em 2021. A taxa de resistência à ceftazidima-avibactam entre isolados do C-Kp resistentes ao ertapenem aumentou de 4,2% em 2019 para 17,2% em 2021. Onze isolados apresentaram novas variantes de KPC designadas KPC-103 a KPC-108 e KPC-139 a KPC-143. Os demais isolados apresentavam variantes de KPC já descritas, sendo a KPC-33 a variante mais frequente (36%). Quinze grupos clonais foram identificados, sendo que a maioria dos isolados pertencia ao ST11. O grupo clonal A foi o mais numeroso e pertencia ao ST258. A principal variante detectada nesse grupo foi a KPC-33. Diferentes grupos de incompatibilidade foram identificados em plasmídeos alberguando blaKPC, sendo os grupos IncN (n=12) e IncF, com replicons FII(K)-FIB (n=11), os grupos mais frequentes, seguido de InX3-IncU (n=9) e IncQ1 (n=1). Dos 46 isolados resistentes à ceftazidima-avibactam, 36 foram capazes de transferir o gene blaKPC para cepas receptoras. A maioria dos isolados foi sensível dose padrão ou sensível aumentabdo exposição ao meropenem e apresentaram redução significativa da CIM quando o avibactam foi adicionado ao aztreonam. O NG-Test CARBA-5 detectou 12 das 24 variantes testadas enquanto que o O.K.N.V.I. RESIST-5 detectou apenas nove variantes. A grande diversidade de variantes KPC, e a predominância do grupo clonal ST11, e da KPC- 33 retratam um cenário preocupante no Brasil

The K. pneumoniae Complex (C-Kp) is the main group of gram-negative bacilli responsible for serious nosocomial infections worldwide and the empirical treatment of these infections usually includes carbapenems. The main mechanism of resistance to this class of antimicrobials is the expression of carbapenemases, and in Brazil, more frequently the KPC type. In March 2019, ceftazidime-avibactam was available for clinical use in Brazil, being widely used to treat infections caused by KPC-producing gram-negative bacilli. Several countries have already reported the presence of KPC-producing K. pneumoniae resistant to ceftazidime-avibactam; however, there are few reports of this occurrence in Brazil. This work aimed to genotypically and phenotypically characterize KPC-producing C-Kp isolates resistant to ceftazidimeavibactam. From July 2019 to July 2021, 46 C-Kp isolates, one per patient, were detected in different sites of infection or surveillance cultures from patients admitted to private hospitals in six Brazilian states. The isolates had their complete genome sequenced on the MiSeq and MinION platforms to determine the allelic variant of blaKPC and evaluate its genetic context. Resistance rates to ertapenem and ceftazidime-avibactam were calculated from a database. The clonality of the isolates was evaluated by PFGE and MLST. The plasmid location of the blaKPC gene was confirmed by conjugation and/or transformation. The minimal inhibitory concentrations for beta-lactams were determined by broth microdilution according to BrCAST. Immunochromatographic assays, NG-Test CARBA-5 and O.K.N.V.I. RESIST-5, were evaluated for its performance in detecting KPC variants. The resistance rate to ertapenem among C-Kp isolates increased from 15.6% in 2019 to 27.3% in 2021. The resistance rate to ceftazidime-avibactam among ertapenem-resistant C-Kp isolates increased from 4.2% in 2019 to 17.2% in 2021. Eleven isolates showed new KPC variants designated KPC-103 to KPC-108 and KPC-139 to KPC-143. The remaining isolates presented previously described KPC variants, with KPC-33 being the most common variant (36%). Fifteen clonal groups were identified, with most isolates belonging to ST11. Different incompatibility groups were identified in plasmids harboring blaKPC, with the IncN (n=12) and IncF groups, with FII(K)-FIB(n=11) replicons, being the most frequent groups, followed by InX3-IncU (n= 9) and IncQ1 (n=1). All IncX3-IncU plasmids were approximately 46 kb in size and were identified among isolates belonging to the largest identified clonal group (A) and ST258. The main variant detected in this group was KPC-33. Of the 46 ceftazidime-avibactam-resistant isolates, 36 were able to transfer the blaKPC gene to recipient strains. Most isolates were susceptible standard dose or susceptible increased exposure to meropenem and showed a significant decrease in MIC when avibactam was added to aztreonam. The NG-Test CARBA-5 was able to detect 12 of the 24 variants evaluated while the O.K.N.V.I. RESIST-5 detected only nine variants. The great diversity of KPC variants, the predominance of the ST11 clonal group, and KPC-33 portray a worrying scenario in Brazil

Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population

Abstract Background In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants. Methods SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression. Results There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05). Conclusions Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA. Key Points Genetic variants of WNT9A were associated with the incidence and severity of TOA. Allele G of rs11588850 was associated with an increased transcriptional activity of WNT9A promoter. Allele G of rs11588850 may add to the risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.

Amplificación de sondas múltiples dependientes de ligación: actualización y revisión del principio, variantes y aplicaciones / Multiplex ligation-dependent probe amplification: update and review of principles, variants, and applications / Amplificação de múltiplas sondas dependentes de ligação: atualização e revisão do princípio, variantes e aplicações

Resumen La amplificación de sondas múltiples dependientes de ligación (MLPA) es una valiosa herramienta en el estudio de alteraciones en el número de copias para distintas patologías de origen genético. La existencia de una amplia oferta de kits comerciales, el fácil y rápido procesamiento de laboratorio, su alta sensibilidad y, en general, los buenos resultados informados han permitido que su uso se encuentre expandido en muchos laboratorios de biología molecular alrededor del mundo. El principio de esta técnica ha sido adaptado para distintas aplicaciones como la MLPA metilación específica para el estudio de enfermedades relacionadas con la impronta epigenética y la MLPA digital que se acopla a equipos de secuenciación de nueva generación para aumentar la cantidad de regiones analizadas en un solo ensayo. Al contar con 10 años de experiencia en el uso de esta técnica en el Laboratorio Nacional de Tamizaje Neonatal y Alto Riesgo se realiza esta revisión con el fin de analizar los principios, variantes de la técnica, análisis de los datos, algunas aplicaciones, ventajas y desventajas de la MLPA en comparación con otras tecnologías disponibles.

Abstract Multiplex ligation-dependent probe amplification (MLPA) is a valuable tool in the study of copy number alterations for different pathologies of genetic origin. The availability of a wide range of commercial kits, the easy and fast laboratory processing, its high sensitivity and, in general, the good results reported have allowed its use to be expanded in many molecular biology laboratories around the world. The basic principle of this technique has been adapted for different applications such as specific methylation MLPA for the study of diseases related to epigenetic imprinting and digital MLPA that is coupled to next-generation sequencing equipment to increase the number of regions analysed in a single trial. With 10 years of experience in the use of this technique, the National Laboratory for Neonatal and High Risk Screening performs this review in order to analyse the principles, variants of the technique, data analysis, some applications, and advantages and disadvantages of MLPA compared to other available technologies.

Resumo A amplificação de múltiplas sondas dependentes de ligação (MLPA) é uma ferramenta valiosa no estudo das alterações do número de cópias para diferentes patologias de origem genética. A existência de uma ampla gama de kits comerciais, processamento laboratorial fácil e rápido, alta sensibilidade e, em geral, os bons resultados relatados, permitiram que seu uso se encontre expandido em muitos laboratórios de biologia molecular ao redor do mundo. O princípio desta técnica foi adaptado para diferentes aplicações como a MLPA metilação específica para o estudo de doenças relacionadas com o imprinting epigenético e a MLPA digital que é acoplada a equipamentos de sequenciamento de nova geração para aumentar o número de regiões analisadas em um único ensaio. Com 10 anos de experiência no uso da técnica, o Laboratório Nacional de Triagem Neonatal e de Alto Risco realiza esta revisão visando a analisar os princípios, variantes da técnica, análise dos dados, algumas aplicações, vantagens e desvantagens da MLPA comparado com outras tecnologias disponíveis.

Evaluación de parámetros inflamatorios, trombóticos y variantes genéticas en pacientes con ataque cerebrovascular isquémico que se asisten en un hospital de Uruguay

Introducción: El ataque cerebrovascular es la segunda causa de muerte en adultos en el mundo occidental y una de las principales causas de discapacidad permanente, aumentando su frecuencia con la edad, el 85 % es de tipo isquémico. Objetivos: Analizar parámetros trombofílicos, hipofibrinolíticos y genéticos en pacientes con ataque cerebrovascular isquémico y evaluar la posible asociación de estos con factores de riesgo cardiovascular. Metodología: Se utilizó un cuestionario para evaluar la presencia de factores de riesgo cardiovascular en 114 pacientes incluidos en el estudio con diagnóstico de ataque cerebrovascular isquémico. Proteína C y antitrombina fueron determinados mediante métodos cromogénicos, resistencia a la proteína C activada e inhibidor lúpico mediante métodos coagulométricos y proteína S libre, inhibidor del activador del plasminógeno-1, homocisteína y lipoproteína (a) por métodos inmunoquímicos. Fibrinógeno fue determinado por coagulometría y proteína C reactiva por inmunoturbidimetría, ambos contra un grupo control. Las variantes genéticas factor V Leiden, protrombina G20210A, rs1205 (gen PCR), rs1800779 (gen NOS3) y rs2257073 (gen ASB10) fueron analizadas mediante real-time PCR, comparando los últimos tres con una población de referencia. La alteración de las frecuencias de las variables fue determinada por análisis estadístico chi-cuadrado. Resultados: Tres de los cuatro pacientes jóvenes estudiados presentaron indicadores de trombofilia. El resto de los parámetros alterados fueron homocisteína 30.1% (22.4-39.1), lipoproteína (a) 32.1% (24.1-41.4), inhibidor del activador del plasminógeno-1 36.0% (27.8-45.1), fibrinógeno 12.3% (7.5-19.6) y proteína C reactiva 78.1% (69.6-84.7). Se encontró asociación (p < 0.05) entre ciertos factores de riesgo cardiovascular y los parámetros evaluados como hipertensión/proteína C reactiva, dislipemia/lipoproteína (a), arritmia/lipoproteína (a) y arritmia/fibrinógeno. Para pacientes con ataque cerebrovascular isquémico solo la variante rs1205 mostró una frecuencia más alta del alelo T. Conclusiones: Este estudio revela la importancia de analizar la trombofilia en pacientes jóvenes, especialmente en aquellos sin factores de riesgo cardiovascular, así como el rol de la hipofibrinolisis, inflamación y algunas variantes genéticas en el desarrollo de ataque cerebro vascular isquémico.

Introduction: Stroke is the second cause of death in adults in the Western world and one of the main causes of permanent disability, increasing in frequency with age; 85% are ischemic. Objectives: To analyze thrombophilic, hypofibrinolytic, inflammatory, and genetic parameters in patients with ischemic stroke and evaluate possible associations with vascular risk factors. Methodology: Questionnaires were used to evaluate vascular risk factors in 114 patients included in the study with ischemic stroke diagnosis. Protein C and Antithrombin were determined by chromogenic assays, Activated Protein C Resistance and Lupus Anticoagulant were determined with by coagulometry and Free Protein S, Plasminogen activator inhibitor-1, Homocysteine and Lipoprotein (a) by immunochemistry. Fibrinogen was assayed by coagulometry and C-reactive protein by immunoturbidimetry, both against a control group. Factor V Leiden, Prothrombin G20210A, rs1205 (CRP gene), rs1800779 (NOS3 gene) and rs2257073 (ASB10 gene) genetic variants were analyzed by Real-Time PCR, comparing the last three with a reference population. Alteration frequencies of the variables were determined by chi-square statistical analysis. Results: Three out of four of the young patients studied presented indicators of thrombophilia. The rest of the altered parameters were Homocysteine 30.1% (22.4-39.1), Lipoprotein (a) 32.1% (24.1-41.4), Plasminogen activator inhibitor-1 36.0% (27.8-45.1), Fibrinogen 12.3% (7.5-19.6) and C-reactive protein 78.1% (69.6-84.7). Associations were found (p<0.05) between certain vascular risk factors and parameters evaluated, namely hypertension/C-reactive protein, dyslipidemia/lipoprotein (a), arrhythmia/lipoprotein (a) and arrhythmia/fibrinogen. For ischemic stroke patients only the genetic variant rs1205 showed higher frequency of the T allele. Conclusions: This study reveals the importance of analyzing thrombophilia in young patients, especially those without vascular risk factors, as well as the role of hypofibrinolysis, inflammation and some genetic variants in the development of ischemic stroke.

Introdução: O AVC é a segunda causa de morte em adultos no mundo ocidental e uma das principais causas de incapacidade permanente, aumentando de frequência com a idade; 85% são isquémicos. Metas: Analisar os parâmetros trombofílicos, hipofibrinolíticos e genéticos em pacientes com acidente vascular cerebral isquêmico e avaliar a possível associação com fatores de risco cardiovascular. Metodologia: Um questionário foi utilizado para avaliar a presença de fatores de risco cardiovascular em 114 pacientes incluídos no estudo com diagnóstico de acidente vascular cerebral isquêmico. Proteína C e antitrombina foram determinadas por métodos cromogênicos, resistência à proteína C ativada e inibidor de lúpus por métodos coagulométricos e proteína S livre, inibidor do ativador do plasminogênio-1, homocisteína e lipoproteína (a) por métodos imunoquímicos. O fibrinogênio foi determinado por coagulometria e a proteína C-reativa por imunoturbidimetria, ambos contra um grupo controle. As variantes genéticas fator V Leiden, protrombina G20210A, rs1205 (gene PCR), rs1800779 (gene NOS3) e rs2257073 (gene ASB10) foram analisadas por PCR em tempo real, comparando as três últimas com uma população de referência. As frequências de alteração das variáveis ​​foram determinadas pela análise estatística qui-quadrado. Resultados: Três dos quatro pacientes jovens estudados apresentaram indicadores de trombofilia. O resto dos parâmetros alterados foram homocisteína 30,1% (22,4-39,1), lipoproteína (a) 32,1% (24,1-41,4), inibidor do ativador de plasminogênio-1 36,0% (27,8-45,1), fibrinogênio 12,3% (7,5-19,6) e proteína C reativa 78,1% (69,6-84,7). Foi encontrada associação (p<0,05) entre alguns fatores de risco cardiovascular e os parâmetros avaliados como hipertensão/proteína C reativa, dislipidemia/lipoproteína (a), arritmia/lipoproteína (a) e arritmia/fibrinogênio. Para pacientes com acidente vascular cerebral isquêmico apenas a variante rs1205 apresentou maior frequência do alelo T. Conclusões: Este estudo revela a importância de analisar a trombofilia em pacientes jovens, especialmente aqueles sem fatores de risco cardiovascular, bem como o papel da hipofibrinólise, inflamação e algumas variantes genéticas no desenvolvimento do acidente vascular cerebral isquêmico.

Análisis comparativo de las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola de la pandemia (REGISTRO ECCOVID) / Comparative analysis of clinical characteristics, evolu tion and mortality of hospitalized patients with COVID-19 during the first and second wave of the pandemic (ECCOVID STUDY)

Resumen Introducción : Las características clínicas y evolutivas de los pacientes con diagnóstico de COVID-19 pueden diferir entre las distintas olas de la pandemia. El objetivo de este estudio fue comparar las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola en Argentina. Métodos : Registro multicéntrico y prospectivo de pacientes ≥ 18 años con diagnóstico confirmado de COVID-19 internados en 18 hospitales de Argentina durante la primera (marzo a octubre 2020) y la segunda ola (marzo a julio 2021) de la pandemia. Se compararon variables demográficas, características clínicas, y evolu ción a 30 días. Resultados : Se incluyeron un total de 1691 pacien tes (primera ola n = 809, segunda ola n = 882). Los pa cientes hospitalizados durante la segunda ola tenían mayor edad (mediana 53 años vs. 61 años, p < 0.001), comorbilidades (71% vs. 77%, p = 0.007) y requerimiento de oxígeno (21% vs. 62%, p < 0.001). Durante la hospi talización, los pacientes de la segunda ola requirieron más oxigenoterapia (49% vs. 85%, p < 0.001), asistencia mecánica respiratoria (12% vs. 22%, p <0,001) y presen taron mayor mortalidad (11% vs. 26%, p < 0.001). Compa rando únicamente a los que requirieron oxigenoterapia durante la hospitalización, la mortalidad a los 30 días fue de 20% y 30% p < 0.001 en la primera y segunda ola respectivamente. Conclusión : Comparados con los pacientes interna dos durante la primera ola, los internados durante la segunda ola de SARS-CoV-2 en Argentina presentaron mayor gravedad y mortalidad.

Abstract Introduction : Clinical features and outcomes of SARS-CoV-2 infections may change between different waves of the pandemic. The objective of this study was to compare clinical characteristics and outcomes between two cohorts of patients hospitalized for COVID-19 during the first and second waves in Argentina. Methods : Multicenter and prospective registry of patients ≥18 years old with a confirmed diagnosis of COVID-19 admitted to 18 hospitals in Argentina during the first wave (March to October 2020) and second wave (March to July 2021) of the pandemic. Demographics, clinical characteristics, and outcomes of these patients were compared. Results : A total of 1691 patients were included (first wave n = 809, second wave n = 882). Hospitalized pa tients during the second wave were older (median 53 years vs. 61 years, p < 0.001), had more comorbidities (71% vs. 77%, p=0.007) and required more supplemental oxygen at admission (21% vs 62%, p < 0.001). During hos pitalization, patients of the second wave required more supplemental oxygen (49% vs. 85%, p < 0.001), invasive ventilation (12% vs. 22%, p < 0.001) and had higher 30- day mortality (11% vs. 26%, p < 0.001). Comparing only patients who required supplemental oxygen during hos pitalization, 30-day mortality was 20% and 30% p < 0.001 for the first and second wave, respectively. Conclusion : Compared to patients admitted during the first wave, patients admitted with SARS-CoV2 dur ing the second wave in Argentina were more seriously ill and had a higher mortality.

The association between VSX1 exon3 gene variants and keratoconus in Malaysian patients

Purpose: This case-control study aims to examine possible associations of VSX1 exon3 gene variants with the development of keratoconus (KC) in Malaysian patients. Methods: A case-control study was done on 42 keratoconus cases, 127 family member controls, and 96 normal controls. Results: Three gene variants, p.A182A, p.P237P, and p.R217H showed significant associations with keratoconus (P < 0.05). While p.A182A and p.P227P were more prevalent than in the family and normal controls (OR 3.14–4.05), the reverse was observed with p.R217H (OR 0.086–1.59). With Haploview analysis, p.A182A and p.P237P were shown to be in linkage disequilibrium (LD) (LOD (logarithm of the odds score) score of 2.0, r2 of 0.957, and 95% confidence interval (CI) of 0.96–1.00). Conclusion: The study results suggest that the p.A182A and p.P237P variants could have contributed to the development of keratoconus in some Malaysians and that these two variants are likely to be co?inherited. In contrast, the p.R217H variant appeared to confer some protection against the development of keratoconus.

Germline Mutations Landscape in a Cohort of the State of Minas Gerais, Brazil, in Patients Who Underwent Genetic Counseling for Gynecological and Breast Cancer / Cenário de mutações germinativas em uma coorte do estado de Minas Gerais, Brasil, em pacientes submetidas ao aconselhamento genético para câncer ginecológico e de mama

Abstract Objective The present study evaluated the profile of germline mutations present in patients who underwent genetic counseling for risk assessment for breast cancer (BC), ovarian cancer (OC), and endometrial cancer (EC) with a possible hereditary pattern. Methods Medical records of 382 patients who underwent genetic counseling after signing an informed consent form were analyzed. A total of 55.76% of patients (213/382) were symptomatic (personal history of cancer), and 44.24% (169/382) were asymptomatic (absence of the disease). The variables analyzed were age, sex, place of birth, personal or family history of BC, OC, EC, as well as other types of cancer associated with hereditary syndromes. The Human Genome Variation Society (HGVS) nomenclature guidelines were used to name the variants, and their biological significance was determined by comparing 11 databases. Results We identified 53 distinct mutations: 29 pathogenic variants, 13 variants of undetermined significance (VUS), and 11 benign. The most frequent mutations were BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T, and BRCA2 c.2T> G. Furthermore, 21 variants appear to have been described for the first time in Brazil. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. Conclusion This study allowed a deeper understanding of the main mutations identified in families in the state of Minas Gerais and demonstrates the need to assess the family history of non-gynecological cancer for risk assessment of BC, OC, and EC. Moreover, it is an effort that contributes to population studies to evaluate the cancer risk mutation profile in Brazil.

Resumo Objetivo O presente estudo avaliou o perfil de mutações germinativas presentes em pacientes submetidas a aconselhamento genético para avaliação de risco para câncer de mama (CM), câncer de ovário (OC) e câncer de endométrio (CE) com possível padrão hereditário. Métodos Foram analisados os prontuários de 382 pacientes que realizaram aconselhamento genético após consentimento informado. Um total de 55,76% dos pacientes (213/382) eram sintomáticos (história pessoal de câncer), e 44,24% (169/382) eram assintomáticos (ausência da doença). As variáveis analisadas foram idade, sexo, naturalidade, história pessoal ou familiar de CM, OC, CE bem como outros tipos de câncer associados a síndromes hereditárias. As diretrizes de nomenclatura da Human Genome Variation Society (HGVS) foram usadas para nomear as variantes e seu significado biológico foi determinado pela comparação de 11 bancos de dados. Resultados Identificamos 53 mutações distintas: 29 variantes patogênicas, 13 variantes de significado indeterminado e 11 benignas. As mutações mais frequentes foram BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T e BRCA2 c.2T > G. Além disso, 21 variantes parecem ter sido descritas pela primeira vez no Brasil. Além das mutações BRCA1/2, foram encontradas variantes em outros genes relacionados a síndromes hereditárias que predispõem a cânceres ginecológicos. Conclusão Este estudo permitiu conhecer melhor as principais mutações identificadas nas famílias do estado de Minas Gerais e demonstra a necessidade de avaliar a história familiar de câncer não ginecológico para avaliação do risco de CM, OC e CE. Além disso, é um esforço que contribui com estudos populacionais para avaliar o perfil de mutações de risco para câncer no Brasil.

Low Expression of E-Cadherin and Cdh1 Variants Associated with Diffuse Gastric Cancer

ABSTRACT Background Reduced or null expression of E-cadherin protein is a frequent cause of diffuse gastric cancer (DGC). More than 50% of patients with DGC present somatic variants in CDH1 gene. Objectives The objectives of this study were to study E-cadherin expression and identify variants in the CDH1 gene in gastric tumors of patients with DGC. Methods We studied 18 Mexican DGC patients who attended a hospital of the Mexican Social Security Institute; E-cadherin expression was determined by immunohistochemistry, and variants were identified by Sanger sequencing in promoter and coding regions. Predictive analysis was performed using PolyPhen-2 and HOPE software. Results We found that 56% of DGC patients showed reduced expression of E-cadherin. All patients carried CDH1 variants; overall, 12 different CDH1 variants were identified. Predictive analysis revealed that the rs114265540 variant was probably damaging, with a value of 0.985, indicating a functional impact on the E-cadherin protein. Variants rs34939176 and rs33964119 were identified as risk factors for DGC (odds' ratios [OR] = 31.3, 95% CI 6.3-154.0, p < 0.001; OR = 6.1, 95% CI 2.0-19.0, p < 0.001, respectively) given their elevated frequency and by comparing it with those reported for MXL population in the 1000 Genomes Project database. Conclusions In this Mexican population, the percentage of diffuse gastric tumors with reduced expression of E-cadherin was similar to that reported in other populations. All gastric tumors of DGC patients studied had somatic CDH1 gene variants; however, the rs114265540, rs34939176, and rs33964119 variants were importantly related to DGC.

Genetics in prenatal diagnosis

The options for prenatal genetic testing have evolved rapidly in the past decade, and advances in sequencing technology now allow genetic diagnoses to be made down to the single-base-pair level, even before the birth of the child. This offers women the opportunity to obtain information regarding the foetus, thereby empowering them to make informed decisions about their pregnancy. As genetic testing becomes increasingly available to women, clinician knowledge and awareness of the options available to women is of great importance. Additionally, comprehensive pretest and posttest genetic counselling about the advantages, pitfalls and limitations of genetic testing should be provided to all women. This review article aims to cover the range of genetic tests currently available in prenatal screening and diagnosis, their current applications and limitations in clinical practice as well as what the future holds for prenatal genetics.

Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China / 生物医学与环境科学（英文）

OBJECTIVE@#This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.@*METHODS@#We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.@*RESULTS@#The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.@*CONCLUSION@#Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

Clinical Study on the Relationship between Gene Mutation Profile and Prognosis in Pediatric Acute Lymphocyte Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance.@*METHODS@#Clinical data of 249 primary pediatric ALL patients diagnosed and treated in the Department of Hematological Oncology of Wuhan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively. Next-generation sequencing (NGS) was used to obtain gene mutation data and analyze the correlation between it and the prognosis of children with ALL.@*RESULTS@#227 (91.2%) were B-ALL, 22 (8.8%) were T-ALL among the 249 cases, and 178 (71.5%) were found to have gene mutations, of which 85 (34.1%) had ≥3 gene mutations. NRAS(23.7%), KRAS (22.9%),FLT3(11.2%), PTPN11(8.8%), CREBBP (7.2%), NOTCH1(6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of NOTCH1 and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ2= 5.573，P＜0.05) and were more likely to have co-mutations (P＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, P＜0.001) and OS rate (53.8% vs 94.1%, P＜0.001) in children with tp53 mutations were significantly lower than those of patients without tp53 mutations. Patients with NOTCH1 mutations had higher initial white blood cell count （128.64×109/L vs 8.23×109/L，P＜0.001）, and children with NOTCH1 mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037).@*CONCLUSION@#Genetic mutations are prevalent in childhood ALL and mutations in tp53 and NOTCH1 are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.

AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

Analysis of clinical characteristics and warning factors in SARS-CoV-2 variants infection / 中国热带医学

@#Abstract: Objective To investigate the influence of the variation of SARS-CoV-2 on the clinical feature, and to provide early warning signs for the variation of SARS-CoV-2 in clinical work. Methods From Jan 2, 2021 to Jun 30, 2021, a total of 105 COVID-19 patients were included in the study using a case-control method. Nasal swab samples were collected from the study subjects, the viral genes were sequenced, and patients were divided into Delta variant group and non-Delta variant group according to their gene sequences. Clinically relevant data were collected from the two groups, and indicators such as days of hospitalization, age distribution, lymphocytes, neutrophils, B lymphocytes, NK cells, IL-4, and IL-10 were compared; subgroup analysis was performed based on the number of days of viral negativity in the study subjects as the basis for grouping, and differences in immunological characteristics were compared, including lymphocytes, neutrophils, B lymphocytes, NK cells, IL-4, IL-10, etc. Results The theoretical hospitalization days of Delta variant group were (22.2±8.33) d, which were significantly longer than (17.6±10.50) d of non-Delta variant group (t=2.396, P<0.05). The total lymphocyte count and IL-4 of Delta variant group were (1.22±0.86) ×109/L and (0.80±0.23) ng/mL, which were significantly lower than corresponding (1.91±0.70) ×109/L and (1.59±0.59) ng/mL of non-Delta variant group (t=4.329, 9.072, P<0.05), while IL-10 was (7.16±7.77) ng/mL, which was significantly higher than (4.26±3.91) ng/mL of non-Delta mutation group (t=1.980, P<0.05). Subgroup analysis showed that the total lymphocyte count and IL-4 concentration in Delta variant group were (1.04±0.60) ×109/L and (0.74±0.25) ng/ml, which were significantly lower than corresponding (1.62±0.56) ×109/L and (1.56±0.52) ng/mL in non-Delta variant group, in patients with delayed discharge (P<0.05). Conclutions SARS-CoV-2 variant has an impact on clinical manifestations. The patient's B cell count and IL-10 concentration increased or IL-2 and IL-4 concentration decreased within 12 hours of admission indicated variant virus infection. The decrease of total lymphocyte count, especially T lymphocyte reduction, strongly suggests discharge delay due to viral clearance disorder.

Research Progress in Antibody Responses Against SARS-CoV-2 Variants of Concern / 中国医学科学院学报

So far,the coronavirus disease 2019(COVID-19)has been persisting for nearly three years,infecting about 700 million people and causing more than 6 million deaths,which has seriously affected the human society.According to Global Initiative on Sharing All Influenza Data,there are more than 12 million SARS-CoV-2 variants,of which the five major variants of concern are Alpha,Beta,Gamma,Delta and Omicron.Their infectivity,pathogencity,and neutralization resistance have changed greatly compared with the original strain,which has brought great pressure to the prevention and control of the pandemic.Antibody level testing is critical for confirming infection,epidemiological investigation,vaccine development,and neutralizing drug preparation.Focusing on the humoral immunity against SARS-CoV-2,this paper introduces the mutation sites,neutralization resistance,and vaccination efficacy of the five variants of concern,and briefly summarizes the evolutionary characteristics,future mutation directions,and host immunity.

Sinonasal anatomy variations on CT scans of a sample of Filipino adults with chronic rhinosinusitis

Objective@#To determine the prevalence of sinonasal anatomic variations seen on paranasal sinus (PNS) CT scans of a sample of Filipino adults with chronic rhinosinusitis.@*Methods@#Design: Cross-sectional study Setting: Tertiary Government Training Hospital Participants: The PNS CT scans of 51 Filipino patients with chronic rhinosinusitis with and without nasal polyposis diagnosed at our outpatien Department of Otorhinolaryngology-Head and Neck Surgery between October 2015 to December 2020 were reviewed for the presence of sinonasal anatomic variants. The prevalence of the identified variants was calculated.@*Results@#The CT scans of 51 patients, 41 (80.4%) men and 10 (19.6%) women, were included. The median age was 48 years (Q25: 35, Q75: 56, IQR:21). The median Lund Mackay Score (LMS) was 15 (Q25: 12, Q75: 20, IQR:8). Majority (94%) had an LMS of ≥5. The most common anatomic variant in the study population was agger nasi (n=46/51, 90.2% present bilaterally) followed by uncinate process attachment to the lamina papyracea (n=90/102, 88.24%). The third to sixth most common findings were Keros type II classification (n=76/102, 74.51%), nasal septal deviation (n=35/51, 68.62%), optic nerve canal type 1 (n=67/102, 65.69%) and anterior ethmoid artery grade 1 (n=46/102, 45.1%), respectively. Less common variants were Onodi cell (n=13/51, 25.49% unilateral and n=10/51, 19.61% bilateral), Haller cell (n=8/51, 15.69% unilateral and n=1/51, 1.96% bilateral), supraorbital cell (n=4/51, 7.84% unilateral and n=4/51, 7.84% bilateral), middle turbinate concha bullosa (n=3/51, 5.88% unilateral and n=6/51, 11.76% bilateral), superior turbinate concha bullosa (n=2/51, 3.92% unilateral and n=1/51, 1.96% bilateral), pneumatized crista galli (n=2/51, 3.92%) and optic nerve dehiscence (n=1/51, 1.96% bilateral). @*Conclusion@#In the adult Filipino population with CRS sampled in this study, the six most common sinonasal anatomic variants were agger nasi, superior attachment of the uncinate process to the lamina papyracea, Keros type II classification, septal deviation, optic nerve canal type 1 and anterior ethmoid artery grade 1. Pre-operatively, the PNS CT scan of every patient must be meticulously evaluated for the sinonasal anatomic variants to avoid surgical complications.