Assessment of Risk Factors for Primary Open-angle Glaucoma

Introduction: primary open-angle glaucoma (POAG) is a chronic and progressive anterior optic neuropathy characterized by perimetric alterations and pathological excavation of the optic disc in the absence of other ocular pathologies or congenital anomalies. It is usually accompanied by an increase in intraocular pressure. Gonioscopic examination confirms that the iridocorneal angle is open. The term "risk factor" is defined as a condition statistically leading to an increased risk of occurrence of an event. The purpose of our work is to list the main risk factors of POAG.Patients and Methods: This is a retrospective study carried out in our ophthalmology department over a period of 4 years between January 2018 and December 2021, involving one hundred patients with POAG followed in glaucoma consultation.Results: These are 100 cases, with an average age of 64.27, with a male predominance. The most found risk factors in our series are: age, intraocular hypertension (IOH), thin cornea, arterial hypertension, diabetes and family history of glaucoma.Conclusion: The identification of the main risk factors of POAG at the individual level is a major data of the management. Knowing these factors helps to monitor patients at risk more carefully and to adjust the treatment more appropriately in patients likely to develop glaucoma or to aggravate already known glaucoma. More efforts are required for early screening and education on POAG in communities, especially in a POAG high-risk population

"Nem tão doentes, nem tão livres de doença": narrativas de mulheres com câncer de mama sobre a investigação da herança genética em um instituto oncológico de pesquisa / "Ni tan enfermas, ni tan libres de la enfermidad": relatos de mujeres con cáncer de mama sobre la investigación de la herencia genética en un instituto de investigación oncológica / "Not so sick, not so disease-free": narratives of women with breast cancer about the investigation of genetic inheritance in an oncological research institute

A tese versa sobre a susceptibilidade hereditária para o câncer de mama sob um olhar socioantropológico. O tema apresenta relevância em função da atual valorização da genética na área da oncologia e dos impactos que esse campo da medicina produz na vida das pessoas e famílias envolvidas. A partir de uma produção etnográfica, buscou-se compreender como a prática do aconselhamento genético interfere em diversos planos da vida de mulheres com câncer de mama hereditário, como o psicoafetivo, social e familiar, atendidas por um instituto oncológico de pesquisa, pertencente ao setor privado de saúde. Para investigação metodológica, utilizou-se um conjunto de dados empíricos: entrevistas semiestruturadas com mulheres com (suspeita de) câncer de mama hereditário, observação de consultas com o serviço de genética e documentos online relativos à hereditariedade da doença na mama. Como resultados, constatou-se de que modos às percepções biomédicas acerca da noção de risco atravessaram a produção de subjetividades, identidades e coletividades das interlocutoras. Outros pontos explorados nas narrativas foram: as repercussões, individuais e coletivas, ocasionadas pela experiência do aconselhamento genético e o entrelaçamento da doença e da hereditariedade a outras vivências de cunho individual. O estudo visou contribuir a dar visibilidade às experiências e as demandas das mulheres investigadas e somar aos estudos risco, biotecnologias e subjetividades.AU

This thesis is about hereditary susceptibility to breast cancer from a socio-anthropological perspective. The theme is relevant due to the current appreciation of the genetics field in the oncological area and the impact on the lives of people and families involved. From an ethnographical starting point, how genetic counselling interferes with the life planning of women with hereditary breast cancer breast in areas such as psycho-affective, social and familiar. The search was conducted in an oncological research institute that belongs to the private healthcare system. For the methodological research, it was used a set of empirical data: semi-structured interviews with (suspected) hereditary breast cancer; participant observation of genetic consultations and online documents related to the heredity of the disease in the breast. As result, it has been noticed how the biomedical perceptions about the notion of risk cross through to the interlocutors' subjective productions, identities and sense of collective. Another aspect of the narratives is the relationship of genetics with oncological illness. It also stands out the individual and collective repercussions caused by the experience of genetic counselling and the intertwining of the disease and heredity with other individual experiences. The study aimed to contribute to giving visibility to the experiences and demands of the women investigated and also to add studies of the risk, biotechnologies and subjectivities.AU

La tesis aborda la susceptibilidad hereditaria al cáncer de mama desde una perspectiva socio-antropológica. El tema es relevante debido a la actual valorización de la genética en el área de la oncología y a los impactos que ese campo de la medicina tiene en la vida de las personas y familias. Con base en una producción etnográfica, buscamos comprender cómo la práctica del asesoramiento genético interfiere en diferentes áreas de la vida de mujeres con cáncer de mama hereditario, como el psicoafectivo, social y familiar, asistidas por un instituto de investigación oncológica, perteneciente al sector privado del cuidado de la salud. La investigación se fundamenta en un conjunto de datos empíricos: entrevistas semiestructuradas con mujeres con (sospecha de) cáncer de mama hereditario, observación de consultas en el servicio de genética y documentos en línea relacionados con la herencia familiar de la enfermedad. Como resultado, se constató como las percepciones sobre la biomedicina sobre la noción de riesgo atraviesan la producción de subjetividades, identidades y colectividades de las interlocutoras. Otros puntos explorados en las narrativas fueron: las repercusiones individuales y colectivas provocadas por la experiencia de la consejería genética y el entrelazamiento de la enfermedad y la herencia con otras experiencias de carácter individual. El estudio pretendió dar visibilidad a las experiencias y demandas de las mujeres investigadas y contribuir a los estudios sobre riesgo, biotecnologías y subjetividades. AU

Genetic recurrence and molecular markers of dyslexia in the Brazilian population

ABSTRACT Purpose: to investigate genetic recurrence and molecular markers for dyslexia in two candidate genes in the Brazilian population. Methods: a cross-sectional, case-control, observational study, with five single nucleotide polymorphisms (SNPs) studied in DYX1C1 and KIAA0319 genes in 86 subjects with dyslexia and 66 controls, matched for gender and age. SNPs were genotyped using the polymerase chain reaction technique in real time, and distribution of genotypic and allelic frequencies between the groups was analyzed. Results: it was determined that 68% of the subjects with dyslexia present a family history of learning difficulties. The DYX1C1 gene did not demonstrate an association with dyslexia, which was found regarding the rs9461045 marker of the KIAA0319 gene. Conclusion: a family history of learning problems was present in more than two-thirds of the group with dyslexia, indicating that this is an important risk factor. An association with dyslexia in the rs9461045 marker was noted, making the study the first one to show an association of the KIAA0319 gene with dyslexia, in Latin America.

Nucleic acid detection and sequence analysis of arboviruses in Xichang / 中华检验医学杂志

Objective:To understand the prevalence of arboviruses in mosquito samples in Xichang City, Sichuan Province, and enrich the data of arbovirus activity and genetic characteristics in southwestern Sichuan Province.Methods:In June 2018, the nucleic acid was extracted from Culex tritaeniorhynchus mosquitoes collected from different pigsties in three villages and suburbs of Xichang City. The specific primers of Yunnan orbivirus, Banna virus, Tibet orbivirus (S7, S10), Flavivirus and alphavirus were used for quantitative polymerase chain reaction examination, and the positive product was cloned for sequencing analysis. Results:A total of 9 012 mosquitoes were collected, of which Cx. tritaeniorhynchus was the dominant species. A number of 88 batches of these mosquitoes were amplified, and 2 strains of Japanese encephalitis virus (JEV), 7 strains of Banna virus (BAV), 7 strains of Tibet orbivirus (TIBOV) and 1 strain of Yunnan orbivirus virus (YOUV) were detected, respectively. By the results of cluster analysis and evolutionary tree analysis, the 17 newly found virus strains were close to the Yunnan isolates, and 2 JEV strains were located in the GI-b clade. The other 7 strains of BAV were A2 evolutionary clades. Of the 7 TIBOV plants, 6 were located in the same clade. One TOUV was in the same clade as the Yunnan strain. Conclusions:Culex tritaeniorhynchus mosquitoes in Xichang city might carry JEV, BAV, YOUV and TIBOV, among them JEV was GI-b type and BAV was A2 type. The results provide data supporting the detection and analysis of arboviruses in Xichang city.

Clinical phenotype and gene mutation analysis of neurodevelopmental disorders caused by CTNNB1 gene mutation / 中华神经科杂志

Objective:To investigate the clinical phenotype and gene mutation in a child with developmental disorders caused by CTNNB1 gene mutation. Methods:Clinical data of a child with CTNNB1 gene mutation who was admitted to Xiamen Hospital of Fudan University Affiliated Pediatric Hospital in May 2017 were collected, whole exome sequencing technology was applied to verify the family lineage of the child, and the pathogenicity of mutation site was analyzed. Results:The patient was a 6 years and 1 month old male, with a clinical phenotype including mental retardation, motor developmental disorders, speech disorders, visual disorders (internal strabismus), microcephaly, and behavioral problems (social withdrawal, overdependence, etc.), as well as panic syndrome (i.e., sudden shrieking in response to auditory and visual stimuli, extensional rigidity of the body, etc., followed by short periods of general extensional rigidity). The whole exome sequencing results showed the presence of a de novo mutation c.283(exon4)C>T in the CTNNB1 gene, and the c.283(exon4)C>T mutation was interpreted as pathogenic (PVS1+PS2+PS1+PM2+PM) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. No relevant genetic variants were found in the parental family verification. Conclusion:CTNNB1 gene mutation c.283(exon4)C>T can cause neurodevelopmental disorders, including mental retardation, motor developmental disorders, speech disorders, visual disorders, microcephaly and behavioral abnormalities.

Agregación familiar para cardiopatía isquémica

RESUMEN Fundamento: la cardiopatía isquémica es una entidad nosológica de origen multifactorial con predisposición genética y susceptible a cambios ambientales. Objetivo: determinar la existencia de agregación familiar para cardiopatía isquémica en pacientes atendidos en consulta de cardiología en el Hospital General Docente Vladimir Ilich Lenin de Holguín. Métodos: se realizó un estudio observacional, analítico de casos y controles (estudio de agregación familiar). La muestra quedó conformada por 60 nuevos pacientes con el diagnóstico de cardiopatía isquémica (casos) y por otros 60 pacientes sin diagnóstico de enfermedad coronaria (controles), pareadas en la razón 1:1. Se emplearon como variables: sexo, edad, antecedentes familiares de cardiopatía isquémica y factores de riesgo ambientales. Se utilizó el estadígrafo Chi cuadrado. Luego se calculó el Odds Ratio para conocer la magnitud de asociación mediante la razón de productos cruzados. Resultados: en el grupo casos existió una mayor frecuencia en el antecedente familiar para cardiopatía isquémica, fue más elevada para los familiares de primer grado con 31 familiares y un 41,3 %. La hiperlipidemia se presentó como el factor de riesgo de mayor frecuencia con 36,7 % en el grupo casos y 37,1 % en el grupo controles. Se determinó un riesgo aproximadamente 4 veces mayor de padecer cardiopatía isquémica en aquellos individuos con historia familiar positiva de primer grado, mientras que los pacientes con hiperlipidemia tienen 4,8 más riesgo de padecer cardiopatía isquémica. Conclusiones: existe agregación familiar para cardiopatía isquémica y se mostró un riesgo mayor de enfermar los pacientes con historia familiar positiva para la enfermedad, principalmente con familiares de primer grado y con hiperlipidemia.

ABSTRACT Background: ischemic heart disease is a nosological entity of multifactorial origin with genetic predisposition and susceptible to environmental changes. Objective: to determine the existence of familial aggregation for ischemic heart disease in patients seen in the cardiology clinic at the Vladimir Ilich Lenin General Teaching Hospital in Holguín. Methods: an analytical observational study of cases and controls (family aggregation study) was carried out. The sample was made up of 60 new patients with a diagnosis of ischemic heart disease (cases) and another 60 patients without a diagnosis of coronary heart disease (controls), paired in a 1:1 ratio. The following variables were used: sex, age, family history of ischemic heart disease and environmental risk factors: smoking, hyperlipidemia, high blood pressure and sedentary lifestyle. The Chi square statistician was used by the Mantel-Haenszel method. The odds ratio (OR) was then calculated to determine the magnitude of association through the ratio of cross products. Results: in the case group there was a higher frequency in the family history for ischemic heart disease, being higher for first degree relatives with 31 relatives and 41.3 %. Hyperlipidemia was the most frequent risk factor with 36.7 % in the case group and 37.1 % in the control group. An approximately 4-fold increased risk of suffering from ischemic heart disease was determined in those individuals with a positive first-degree family history, while patients with hyperlipidemia have a 4.8 times greater risk of suffering from ischemic heart disease. Conclusions: there is family aggregation for ischemic heart disease and a higher risk of getting sick was shown in patients with a positive family history for the disease, mainly with first-degree relatives and with hyperlipidemia.

Incontinencia pigmentaria / Incontinentia pigmenti

RESUMEN La incontinencia pigmentaria es una genodermatosis de rara presentación, que es considerada una alteración hereditaria, ligada al cromosoma X, con carácter dominante. Se presenta con mayor frecuencia en mujeres, y el compromiso principal se observa en tejidos derivados del ectodermo; es decir, puede evidenciarse como anormalidades en piel, dientes, pelos, ojos y sistema nervioso. Se presenta un caso de incontinencia pigmentaria con manifestaciones cutáneas en un recién nacido varón. El caso se confirmó a través de dos biopsias evaluadas en el servicio de anatomía patológica del Hospital Cayetano Heredia. Debido al espectro amplio de presentación clínica de incontinencia pigmentaria, se recomienda considerar a esta entidad en el diagnóstico diferencial cuando nos encontramos frente a lesiones cutáneas, predominantemente vesiculares y que siguen una distribución siguiendo las líneas de Blaschko. La incontinencia pigmentaria es una enfermedad infrecuente en nuestro país, y su diagnóstico requiere de una adecuada correlación clínico patológica, y del conocimiento de las distintas fases de la enfermedad. El diagnóstico y reconocimiento oportuno y temprano de la entidad permitirá prevenir complicaciones asociadas a nivel sistémico.

ABSTRACT Incontinentia Pigmenti is a rare genodermatosis, which is considered a hereditary alteration, linked to the X chromosome, with a dominant character. It occurs more frequently in women, and the main involvement is observed in tissues derived from the ectoderm, that is, it can be seen as abnormalities in the skin, teeth, hair, eyes and nervous system. We report a case of incontinentia pigmenti with cutaneous manifestations in a male newborn is presented. The case was confirmed through two biopsies evaluated in the pathological anatomy service of the Cayetano Heredia Hospital. Due to the broad spectrum of clinical presentation of incontinence pigmenti, it is recommended to consider this entity in the differential diagnosis when we are faced with predominantly vesicular skin lesions that follow a distribution along Blaschko lines. Incontinentia pigmenti is a rare disease in our country, and its diagnosis requires an adequate clinicopathological correlation, and knowledge of the different phases of the disease. The timely and early diagnosis and recognition of the entity will prevent associated complications at the systemic level.

Family History of Hypertension: Impact on Blood Pressure, Anthropometric Measurements and Physical Activity Level in Schoolchildren

Abstract Background: A family history of arterial hypertension (AH), combined with environmental risk factors, is directly related to the development of AH. Objectives: To evaluate the frequency of AH, anthropometric indicators and level of physical activity and their association with a family history (FH) of AH in school children. Methods: Cross-sectional study with 118 students, aged between 11 and 17 years, of both sexes. Waist circumference (WC), weight, height, level of physical activity and FH of HA were collected. Body mass index z score (BMI-z) and waist-to-height ratio (WHtR) were calculated. Binary logistic regression model was used to verify the chance risk, with significance p <0.05. Results: Of the 118 parents who answered the questionnaire, 34.7% had a positive FH of AH. Girls with a positive FH had higher means of WC (p= 0,004), BMI (p=0,020), and systolic blood pressure (SBP) (p=0,006) than boys, and a higher risk of being overweight (OR=4,48; 95%CI:1,55-12,94), and having elevated WHtR (OR=5.98; 95%CI:1.66- 21.47) and SBP (OR=3,07; 95%CI:1,03-9,13) than girls without a FH, but they practice more vigorours moderate physical activity (MVPA) (p=0,039). On the other hand, no differences in these parameters were observed between boys with and without a FM of AH. Conclusion: Overweight and a FH of hypertension were associated with an increased risk for AH in girls. This was not observed among boys, perhaps due to more active lifestyle.

Mutación heterocigota, autosómica recesiva del gen RARS2 en una paciente colombiana de padres no consanguíneos / Autosomal recessive heterocygote mutation of the RARS2 gene in a colombian patient with non- consanguineous parents

Las nuevas metodologías de secuenciación masiva han permitido caracterizar e identificar variantes genéticas asociadas a diferentes patologías. En este trabajo se presenta el caso de una paciente con una mutación del gen RARS2 que codifica la enzima arginino-ARNt ligasa para la codificación de proteínas. Esta alteración genética se manifiesta en hipoplasia pontocerebelosa tipo 6, con una prevalencia de <1/1 000 0000, caracterizada por un cerebelo y un puente de menor tamaño asociados a un retraso grave en el neurodesarrollo. El análisis de caso permite un mejor conocimiento de enfermedades de origen genético, específicamente, de aquellas con patrones de herencia autosómicos recesivos de padres no consanguíneos. Su estudio sobre todo en lo relacionado con el ámbito familiar y socioeconómico, y su base genética, ayuda a una mejor calidad de vida de los pacientes y su familia.

The latest method of next-generation sequencing has allowed the characterization and identification of genetic variants associated to diverse pathologies. In this article, we present the case of female patient with a mutation of the RARS2 gene that encodes the enzyme for arginyl tRNA synthetase for coding of proteins. This genetic alteration manifests in pontocerebellar hypoplasia type 6, with a prevalence of <1/1,000,0000, characterized by a cerebellum and pons that are smaller in size and are associated with severe neurodevelopmental delay. The analysis of the case of this patient provides better knowledge of diseases of genetic origin; specifically, regarding genetic diseases of autosomal recessive patterns of inheritance from non-consanguineous parents. The impact of these studies; specially within the family, social, economic and genetic aspects helps provide a better quality of life for these patients and their family.

Correlation between HLA-Cw*0602 and LCE3B_LCE3C-del allele interaction and psoriasis vulgaris in a population of Mongolian nationality in Inner Mongolia / 中国基层医药

Objective:To investigate the effect of HLA-Cw*0602 and LCE3B_LCE3C-del allele interaction on the risk of psoriasis vulgaris in a population of Mongolian nationality in Inner Mongolia. Methods:A total of 365 Mongolian patients with psoriasis vulgaris who received treatment in The Affiliated Hospital of Inner Mongolia Medical University from January 2006 to December 2015 (case group) and 284 healthy subjects who concurrently received physical examination in the same hospital (control group) were included in this study. After sex and age matching, and quality control, the correlations between HLA-Cw*0602 and LCE3B_LCE3C-del allele and psoriasis vulgaris in a population of Mongolian nationality were analyzed using SPSS 20.0 software. The interaction between HLA-Cw*0602 and LCE3B_LCE3C-del alleles (adjusting for potential confounders including age and sex) was analyzed using logistic regression. Results:Logistic regression interaction item Int of dominant inheritance mode HLA-Cw*0602 allele and recessive inheritance mode LCE3C_LCE3B-del allele revealed OR = 2.38, P = 0.033, and interaction index S = 1.21, indicating that there was a synergistic effect between the two alleles. Conclusion:The co-existence of HLA-Cw*0602 and LCE3B_LCE3C-del may increase the risk of psoriasis vulgaris in a population of Mongolian nationality in Inner Mongolia.

Clinical characteristics and gene analysis of one case of glycogen storage disease type Ⅱ / 中国基层医药

Objective:To investigate the key points of diagnosis and treatment of glycogen storage disease type Ⅱ(GSD Ⅱ).Methods:The clinical data of one child patient with GSD Ⅱ who received treatment in Hainan Children's Hospital on May 7, 2017 were retrospectively analyzed.Results:The child presented with atypical clinical manifestations, including pneumonia first, accompanied by muscle weakness and elevated muscle enzymes. Whole-genome sequencing showed that there were two heterozygous mutations in the acid alpha-glucosidase (GAA) gene, c.871C > T and c.1447G > A. The child was diagnosed with GSD Ⅱ.Conclusion:GSD Ⅱ has atypical clinical manifestations. It is easily misdiagnosed. Early whole-genome sequencing is helpful for the diagnosis of GSD Ⅱ.

Research progress on interleukin-10 receptor A in the pathogenesis of inflammatory bowel disease / 中国小儿急救医学

Inflammatory bowel disease(IBD) is a complex multifactorial disease characterized by chronic recurrent intestinal inflammation.The etiology of IBD has not yet been determined, and relevant studies have focused on the genetic susceptibility, immune response, intestinal microbiome and environmental factors of the host.Studies have found that interleukin-10 receptor A(IL-10RA)plays important roles in the pathogenesis of IBD.IL-10RA can not only affect the intestinal barrier, but also affect the intestinal immune system.Furthermore, the mutation of IL-10RA itself is highly correlated with very early-onset IBD.

(Lack of) knowledge of mothers about sickle cell trait and disease: a qualitative study / El (des) conocimiento de las madres sobre células falciformes y anemia falciforme: un estudio cualitativo / O (des)conhecimento das mães sobre o traço e a doença falciforme: um estudo qualitativo

ABSTRACT Objective: to analyze the understanding of mothers about sickle cell disease and/or trait of the family from a diagnosed child. Methods: this is a qualitative study, using a semi-structured interview with 23 mothers, at a sickle cell disease outpatient clinic of a public institution, from October to December 2017. Analysis was thematic. Results: all participants had sickle cell trait as well as the parents of their children. Twenty children were diagnosed with sickle cell disease by Heel Prick Test, and three, after hospitalization due to the disease. Most did not know how to report the presence of the trait or disease in relatives other than nuclear. Final considerations: diagnosis cannot be restricted to the result of neonatal screening, requiring that preventive information on sickle cell crises be reinforced. It is recommended to search for other affected relatives to learn about their genetic condition, reflecting on their reproductive decisions.

RESUMEN Objetivo: analizar el entendimiento de las madres sobre células y/o anemia falciformes de la familia del niño diagnosticado. Métodos: se trata de un estudio cualitativo, mediante entrevista semiestructurada a 23 madres, en el ambulatorio de anemia falciforme de una institución pública, de octubre a diciembre de 2017. El análisis fue temático. Resultados: todos los participantes tenían células falciformes, así como los padres de sus hijos. Veinte niños fueron diagnosticados con anemia de células falciformes mediante la prueba de punción del talón y tres, después de la hospitalización debido a la enfermedad. La mayoría no sabía cómo informar la presencia de células o anemia en miembros de la familia distintos del nuclear. Consideraciones finales: el diagnóstico no puede restringirse al resultado del cribado neonatal, requiriendo que se refuerce la información preventiva sobre las crisis drepanocíticas. Se recomienda buscar a otros familiares afectados para conocer su condición genética, reflexionando sobre sus decisiones reproductivas.

RESUMO Objetivo: analisar o entendimento de mães acerca da condição do traço e/ou doença falciforme da família a partir da criança diagnosticada. Métodos: trata-se de um estudo qualitativo, sendo utilizada entrevista semiestruturada, com 23 mães, no ambulatório de doença falciforme de uma instituição pública, no período de outubro a dezembro de 2017. A análise foi temática. Resultados: todos os participantes tinham traço falciforme, bem como os pais dos seus filhos. Vinte crianças foram diagnosticadas com doença falciforme pelo teste do pezinho, e três, após hospitalização decorrente da doença. A maioria não sabia informar a presença do traço ou doença em outros membros da família que não a nuclear. Considerações finais: o diagnóstico não pode ficar restrito ao resultado da triagem neonatal, necessitando que as informações preventivas de crises falcêmicas sejam reforçadas. Recomenda-se a busca de outros membros da família afetados para conhecimento da sua condição genética, refletindo sobre suas decisões reprodutivas.

The genetic distribution in Chinese patients with Charcot-Marie-Tooth diseases: a 14-year cohort study / 中华神经科杂志

Objective:To investigate the genetic distribution of pathogenic genes of Charcot-Marie-Tooth diseases (CMT) in Chinese Han population, and compare the similarity and difference with the data in Peking University Third Hospital in 2013.Methods:Five hundred and twenty families with CMT and related diseases in Peking University Third Hospital and China-Japan Friendship Hospital from January 2007 to March 2021 were collected. After peripheral myelin protein 22 (PMP22) gene duplication and deletion mutations were initially detected by multiple ligation probe amplification, the probands of these families were sequenced by next-generation sequencing (NGS) gene panel or whole exome sequencing, and validated by Sanger sequencing.Results:Among the 520 families, 336 CMT families were genetically confirmed, and the mutation detection rate increased from 48.6% (51/105) in 2013 to 64.6% (336/520) in 2021 (χ 2=9.54, P=0.003). Among them, 139 families had PMP22 gene duplication mutation (139/520, 26.7%), 46 families had gap junction beta-1 (GJB1) gene mutation (46/520, 8.8%), 26 families had mitofusin-2 (MFN2) gene mutation (26/520, 5.0%), 12 families had myelin protein zero (MPZ) gene mutation (12/520, 2.3%), 11 families had PMP22 gene point mutation (11/520, 2.1%), and 10 families had heat shock protein B1 gene mutation (10/520, 1.9%). There were 10 families with ganglioside induced differentiation associated protein 1 (GDAP1) gene mutation (10/520, 1.9%), 8 families with SH3 domain and tetratricopeptide repeats 2 (SH3TC2) gene mutation (8/520, 1.5%), 7 families with immunoglobulin mu DNA binding protein 2 (IGHMBP2) gene mutation (7/520, 1.3%), 6 families with MORC family CW-type zinc finger 2 (MORC2) gene mutation (6/520, 1.2%), 5 families with sorbitol dehydrogenase (SORD) gene mutation (5/520, 1.0%), 16 families with very rare gene mutation (16/520, 3.1%) and 184 families without genetic diagnosis (184/520, 35.4%). Conclusions:Compared with the results in 2013, the 3 most common genes affecting CMT were still PMP22, GJB1 and MFN2 genes, but the proportion difference of patients with MPZ gene mutation gradually decreased with other genes such as SH3TC2 and GDAP1 genes. The proportion of newly discovered CMT genes, such as MORC2 and SORD genes, was similar with IGHMBP2 gene, which should be paid more attention. NGS greatly improved the detection rate of CMT, especially for patients with autosomal recessive-CMT.

Clinical characteristics and genetic analysis of a pedigree with Stargardt disease caused by a novel mutation in ABCA4 gene / 中华检验医学杂志

Objective:To explore the clinical characteristics and genetics of a pedigree with Stargardt disease, and investigate the pathogenicity of ABCA4 (ATP binding cassette subfamily A member 4) gene mutations in Stargardt disease.Methods:The proband was admitted to the Second People′s Hospital of Jinan in May 2021 due to diminution of vision. The proband was diagnosed with Stargardt disease according to the clinical diagnostic criteria of Stargardt disease. Detailed ophthalmological examinations was also performed on family members of the proband. Genomic DNA were extracted from the proband and the family members, and the whole exon sequencing was performed to find pathogenic gene mutations. The hazard of mutations was analyzed by polyphen-2, SIFT and MutationTaster websites. Sanger sequencing was used to verify the mutations. Conserved analysis of homologous species and 3-dimensional (3D) molecular model of the protein were used to analyze the pathogenicity.Results:Ophthalmological examinations showed reduced binocular vision, macular atrophy and "bull′s eye sign" in the proband and there was no abnormal signs and symptoms among the family members. Through whole exon sequencing analysis and Sanger sequencing verification, the compound heterozygous mutations (c.215G>A and c.6563T>C) of ABCA4 gene were co-segregated with this disease in this family. SIFT, Polyphen-2 and MutationTaster predicted that these two mutations were pathogenic. Conservative analysis and 3D molecular model of protein showed that mutations could cause changes in protein structure and affect protein function.Conclusion:The compound heterozygous mutations (C.215G>A and C.6563T>C) of ABCA4 gene are the pathogenic mutations of Stargardt disease in this pedigree.

Analysis of cerebral infarction due to inherited dysplasminogenemia / 中华神经科杂志

Objective:To investigate the relationship between inherited dysplasminogenemia and cerebral infarction (CI) by phenotype and gene mutation analysis of 2 inherited dysplasminogenemia pedigrees.Methods:Retrospective analysis was carried out on clinical data of 2 patients diagnosed with CI who were treated in the Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University in January and March 2021, and peripheral venous blood samples were collected from proband 1 and his family members (8 subjects, 4 generations in total) and proband 2 and her family members (5 subjects of 3 generations in total), and their plasminogen (PLG) activity (PLG:A), protein C activity, protein S activity, antithrombin activity and the content of PLG antigen (PLG: Ag), fibrinogen, D-dimer and fibrinogen degradation products were measured for definite diagnosis. All 19 exons,5′ and 3′ untranslated regions of PLG were amplified with polymerase chain reaction, and the amplification products were analyzed by direct DNA sequencing. The results were compared with human PLG reference sequences published in the National Center for Biotechnology Information database using Chromas software to find the mutation sites, and confirmed by reverse sequencing.Results:Both of the 2 patients with confirmed CI had a young onset, and PLG: A was reduced to 21% in the proband 1 and to about 50% in 4 family members; PLG: A was reduced to about 50% in the proband 2 and 2 family members; PLG:Ag and the above tests were essentially normal in both probands and family members. Gene analysis showed that the proband 1 had the homozygous mutation of c.1858G>A in exon 15, the 4 family members of the proband 1, proband 2 and her 2 family members had the heterozygous mutation of c.1858G>A in exon 15, which resulted in a mutation of alanine at position 620 in PLG to threonine (p.Ala620Thr).Conclusions:The decrease of PLG:A was caused by the p.Ala620Thr missense mutation of PLG gene. Proband having CI may be related to the inhibition of fibrinolytic function in the organism due to the p.Ala620Thr missense mutation.

Research progress on familial episodic pain syndrome / 中华神经科杂志

Familial episodic pain syndrome is characterized by ion channel gene mutation in dorsal root ganglion neurons, and there can be neuropathic pain in different parts. However, the lack of awareness of familial episodic pain syndrome, along with the absence of uniform diagnostic and treatment standards, may lead to frequent missed diagnosis and misdiagnosis. This article will review the concepts, classification, pathogenesis, clinical features, diagnosis and treatment of familial episodic pain syndrome, aimed at deepening the understanding of the diseases as well as facilitating early diagnosis and treatment.

Some thoughts on hereditary dermatoses / 中华皮肤科杂志

Genodermatology is an important branch of dermatology. The Chinese dermatological community has made many achievements in the field of hereditary skin diseases, and a number of professional research institutions and teams have been internationally known. Under the social and technological background of the new era, the diagnosis and treatment patterns for hereditary dermatoses are expected to be developed according to national regulations and social needs. The author shares some thoughts on this field, in order to facilitate the research in, as well as diagnosis and treatment of hereditary skin diseases.

Genetic susceptibility genes and clinical features of early-onset breast cancer / 国际肿瘤学杂志

Objective:To explore the germline mutation frequency of genetic susceptibility genes and clinical characteristics in early-onset breast cancer (onset age ≤35 years) in China.Methods:Clinical information and peripheral blood of 150 patients aged 35 and younger diagnosed with breast cancer in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to December 31, 2019 were collected. Then DNA was extracted to detect germline mutations in breast cancer susceptibility gene (BRCA) 1, BRCA2, ataxia telangiectasia mutated (ATM) , partner and localizer of BRCA2 (PALB2) , tumor protein 53 (TP53) and cell cycle checkpoint kinase 2 (CHEK2) genes. Mutations were interpreted as pathogenic, likely pathogenic, uncertain significance, likely benign and benign according to the classification criteria and guidelines for genetic variation. Patients were divided into mutation group ( n=18) and non-mutation group ( n=132) according to the presence or absence of pathogenic or probable pathogenic germline mutations, and the χ2 test was used to analyze the relationships between genetic susceptibility gene mutations and clinicopathological characteristics. Results:Eighteen pathogenic or likely pathogenic germline mutations were detected in 150 patients with early-onset breast cancer, for an overall mutation frequency of 12.0%. Among them, there were 8 (5.3%) BRCA2 mutation, 7 (4.7%) BRCA1 mutation, 1 (0.7%) PALB2 mutation, and 2 (1.3%) TP53 mutation. There were no pathogenic or likely pathogenic variants in ATM and CHEK2 genes. The mutation type was dominated by frameshift mutation (9/18, 50.0%) , followed by nonsense mutation (7/18, 38.9%) , missense mutation (1/18, 5.6%) and splice acceptor mutation (1/18, 5.6%) . Among the molecular subtypes of 18 mutation carriers, 9 cases were Luminal B, 6 cases were triple negative breast cancer (TNBC) , 2 cases were Luminal A, and only 1 case was human epidermal growth factor receptor-2 (HER-2) amplification. Among them, 8 BRCA2 mutation carriers were Luminal type, and 6 of 7 BRCA1 mutation carriers were TNBC type. There were no statistical differences in family history of breast cancer ( P=0.343) , estrogen receptor (ER) status ( χ2=0.16, P=0.688) , HER-2 status ( χ2=2.89, P=0.089) , molecular subtype ( χ2=1.99, P=0.575) , and initial diagnosis TNM stage ( χ2=2.49, P=0.115) between the mutation group and the non-mutation group. Conclusion:The patients with early-onset breast cancer have high frequency of germline mutations. It is recommended that patients with early-onset breast cancer undergo genetic counseling and multigene testing.