A case report of congenital dysplasia caused by the ANK3 gene mutation in the newborn / 中华实用儿科临床杂志

The clinical features, examination findings and gene results of the newborn diagnosed with congenital dysplasia by the ANK3 gene heterozygous mutation in the First Hospital of Jilin University were retrospectively analyzed.A female newborn at 10 minutes presented for postnatal asphyxia and 10 minutes after resuscitation.She had a special appearance, with little spontaneous breathing, no swallowing, extremely low muscular tension, and no primal reflexes.Amplitude integrated electroencephalogram(aEEG) suggested the burst suppression (BS) background activity, BS (+ ), lower boundary at 2 μV, upper boundary at 50 μV, no sleep awakening cycle, no convulsive seizure, and mechanical brush seen in the original electroencephalogram burst.Severe abnormal aEEG was detected.Gene results suggested 2 heterozygous mutations in the ANK3 gene [c.4183(exon33) C >G and c. 8239(exon37) C >T], which have not been previously reported.This case report for the first time reported the clinical phenotype of the ANK3 gene mutation in the newborn with congenital dysplasia.

Clinical characterization and genetic analysis of 5 Chinese families with glucokinase gene mutations / 中华内分泌代谢杂志

Objective:To summarize the clinical manifestations and molecular genetic characteristics of 5 families with maturity-onset diabetes mellitus of the young 2 (MODY2) caused by glucokinase (GCK) gene mutations.Methods:Clinical data and biochemical results of probands were collected. Peripheral blood samples of probands and first-degree family members were collected and whole exome gene was detected using second-generation sequencing. After comparing against the database, the suspected pathogenic sites were selected for Sanger sequencing verification.Results:All the 5 probands presented with mild fasting hyperglycemia, HbA 1C<7.5%, and no symptoms of thirst, polydipsia or polyuria. There were 6 mutants in 5 families, including M1: c.555delT (P.leu186CysFS Ter19) and M3: c. 263T>A (p.Met88Lys) which haven′t been reported before. During the follow-up, all probands received life-style intervention, except 2 pregnant women who should consider insulin treatment if necessary according to fetal genotypes. Conclusion:Among patients who meet the diagnostic criteria for MODY, MODY2 screening should be performed for children or pregnant women with mild hyperglycemia and family history. GCK gene detection is the gold standard for diagnosis, and accurate diagnosis will be conducive to the selection of appropriate treatment.

Development of the patient-derived xenograft model for gallbladder carcinoma and gene screening for tumor associated mutations / 中华肝胆外科杂志

Objective:To establish a patient-derived xenograft (PDX) model of gallbladder carcinoma (GBC) and to screen mutated genes associated with GBC with the aim to provide an effective preclinical model with novel therapeutic targets for individualized patient treatment.Methods:The PDX model of GBC was established by transplantation of fresh GBC tissues from 10 patients into subcutaneous tissues of nude mice. In two of these mice, the PDX tumor tissues were stained with HE, Ki67 immunohistochemical staining and whole exome sequencing (WES). The biological characteristics of the PDX tumor tissues were compared with those of the primary donor tumors in histological structure and molecular pathology, and a high-throughput screening of tumor mutation genes was then carried out.Results:In this study, the success rate of the PDX model of GBC was 70% (7/10). The pathological and growth characteristics of PDX tumor tissues and donor tumors were basically similar. In the 2 modeled cases sequenced by WES, the same rates between the harmful mutant genes in the PDX model and primary donor tumor were 71.4% (15/21) and 65.2% (15/23), and the same genes accounted for 93.8% (15/16) and 71.4% (15/21) in the harmful mutant gene of the PDX model. The 22 mutated genes, including TP53, ABCC4 and AMPD1, were involved both in the two donor tumors, and the model tumor tissues. Ten genes including TP53 and ABCC4 were screened out and they might be closely related to development of GBC by bioinformatics analysis.Conclusions:The PDX model of GBC could effectively be used in patients with GBC in this preclinical study on individualized patient treatment. In addition, 10 mutated genes, including TP53 and ABCC4 and the like, may be used as new potential therapeutic targets for GBC.

Scrub typhus leading to focal segmental glomerulosclerosis in a child due to genetic predisposition

Scrub typhus is a multisystem disease, caused by genera orientia tsutsugamushi and is currently endemic in India. In children, the disease may vary from a mild to a severe form. Complications include encephalitis, myocarditis, disseminated intravascular coagulation, acute kidney injury, atypical pneumonia, etc. The pathophysiologic mechanisms of renal involvement in scrub typhus include prerenal failure, septic shock, vasculitis, acute tubular injury and direct renal invasion by rickettsia. Here, authors present the case of a previously well 5-year old female child who was admitted to our hospital with a history of high-grade fever and pain abdomen. IgM scrub typhus turned out to be positive and she was adequately treated with doxycycline. She turned afebrile but then gradually developed anasarca, hematuria, proteinuria and persistent stage 2 hypertension. Kidney biopsy was done which revealed focal segmental glomerulosclerosis (FSGS). Further workup of the patient by whole exome sequencing revealed missense mutations in TBX18, INF2 and NPHS1 genes. Mutations in INF2 gene is a recently discovered cause of autosomal dominant FSGS. In our case, the scrub typhus mediated kidney injury probably acted as a trigger in unmasking FSGS in the already genetically susceptible child.

Detection of MSX1 gene mutations in patients with congenital tooth loss in Van der Woude syndrome / 口腔疾病防治

Objective@#To explore the relationship between MSX1 gene detection and tooth loss in a Van der Woude syndrome (VWS) family @* Methods @# DNA was extracted from the venous blood of 2 patients with dental hy⁃podontia in the 9th family of Van der Woude syndrome (VWS) families and 62 controls with complete dentition. Primers were designed for the MSXl gene. The coding regions of exons 1 and 2 of the MSX1 gene were amplified by PCR. The purified products of exons 1 and 2 of the MSX1 gene were sequenced and analyzed by sequence alignment @*Results@#The ivs2+68 C>T polymorphism in the MSX1 gene was found in the VWS9 members with tooth loss, and the VWS pa⁃tients with IRF6 gene mutations had increased tooth loss@* Conclusion@#Congenital tooth loss in the patients with con⁃genital missing teeth in VWS family 9 may be related to the ivs2 + 68 C> T polymorphism of the MSX1 gene.

Clinical Value of Droplet Digital PCR and Super-ARMS Detection of Epidermal Growth Factor Receptor Gene Mutation in Plasma Circulating Tumor DNA of Patients with Advanced Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#The patients with advanced lung adenocarcinoma should select targeted drugs based on the type of tumor epidermal growth factor receptor (EGFR) gene mutation. However, it is difficult to collect tumor tissue of advanced lung adenocarcinoma, and some experts agree that peripheral blood can be used as a substitute for tumor tissue as a test specimen. This paper aimed to investigate the clinical value of ddPCR and super-amplification refractory mutation system (ARMS) in detecting EGFR gene mutation in peripheral blood of patients with advanced lung adenocarcinoma.@*METHODS@#A total of 119 patients diagnosed in Beijing Chest Hospital Affiliated to Capital Medical University from February 2016 to February 2019 were collected, and the sensitivity and specificity of plasma ctDNA EGFR gene mutation detected by ddPCR and super-arms were compared. Some patients with positive EGFR gene mutations received oral treatment with first-line EGFR tyrosine kinase inhibitors (EGFR-TKI). The patients were divided into subgroups according to the test results. In group 1, both ddPCR and super-arms showed positive EGFR gene mutation results, with 21 cases. In group 2, ddPCR and super-arms detection of EGFR gene mutation were all negative, with 16 cases. In group 3, the ddPCR test was positive and the super-arms test was negative, with 5 cases. In group 4, the ddPCR test result was negative while the super-arms test result was positive. Since the number of patients in group 4 was 0, no statistics were included. Objective response rate (ORR) and disease control rate (DCR) were used to evaluate the short-term outcome, and progression-free survival (PFS) was compared with survival analysis to evaluate the long-term outcome.@*RESULTS@#EGFR mutations were detected in 58 (48.7%) of 119 patients with advanced lung adenocarcinoma. The coincidence rate between ddPCR and EGFR gene mutation in tumor tissues was 82.4% (Kappa=0.647, P0.05). Survival analysis showed that the PFS of the three groups was compared. The difference was not statistically significant (χ²=2.221, P=0.329).@*CONCLUSIONS@#ddPCR, as a high sensitivity and specificity liquid gene detection method, can be used as a reliable method to detect the mutation of plasma ctDNA EGFR gene in patients with advanced lung adenocarcinoma. The results of plasma genetic testing can also be used as the basis for predicting the efficacy of EGFR-TKIs in patients.

Incidencia de mutaciones genéticas en pacientes con cáncer de mama y ovario con patrón de origen hereditario / Incidence of genetic mutations in patients with breast cancer and ovarian cancer with hereditary pattern

Resumen OBJETIVO: Determinar las mutaciones genéticas en el cáncer de mama de patrón hereditario y demostrar si existe alguna asociación significativa entre las más comunes en población mexicana y el riesgo de padecerlo. MATERIALES Y MÉTODOS: Estudio transversal y observacional efectuado en el Hospital Ángeles México en coordinación con el Instituto Nacional de Medicina Genómica. Criterios de inclusión: pacientes con cáncer de mama y uno o más familiares de primer grado afectados por esta enfermedad y pacientes con cáncer de ovario. Criterios de exclusión: pacientes sin antecedentes de cáncer de mama ni ovario, o con algún familiar en el protocolo. Se empleó la técnica de rearreglos en placas RT2 Profiler para Master-Mix Quantinova probe PCR kit. Para el análisis estadístico se utilizó el programa SPSS versión 22 y Epi Info versión 7. RESULTADOS: Se estudiaron 39 pacientes con edad promedio de 53.2 ± 12.1 años. Los receptores de progesterona y estrógeno no mostraron diferencia entre grupos. Hubo mayor tendencia para BRCA1. Al estudiar las mutaciones con significación estadística, en las que sobresalieron los casos de BRCA2 versus sin significación y los casos negativos, no hubo diferencia estadística significativa, pero con una tendencia a mayor frecuencia de BCRA1. Al evaluar las estirpes de cáncer de mama y los grados nucleares comparados por edad, los tres grupos de grado nuclear comparados por edad mostraron diferencias. CONCLUSIÓN: Los datos obtenidos muestran que en la población mexicana el gen BRCA2 es el de mayor incidencia de cáncer hereditario, en edad de aparición más temprana y mayor grado nuclear al momento del diagnóstico.

Abstract OBJECTIVE: To determine the genetic mutations in hereditary pattern breast cancer and demonstrate whether there is a significant association between the most common in the Mexican population and the risk of suffering it. MATERIALS AND METHODS: Cross-sectional and observational study conducted at the Hospital Angeles México in coordination with the National Institute of Genomic Medicine. Inclusion criteria: patients with breast cancer and one or more first-degree relatives affected by this disease and patients with ovarian cancer. Exclusion criteria: patients without a history of breast or ovarian cancer, or with a family member in the protocol. The RT2 Profiler plate rearrangement technique was used for Master-Mix Quantinova probe PCR kit. The SPSS version 22 program and Epi Info version 7 were used for the statistical analysis. RESULTS: 39 patients with an average age of 53.2 ± 12.1 years were studied. Progesterone and estrogen receptors showed no difference between groups. There was a greater trend for BRCA1. When studying the mutations with statistical significance, in which the cases of BRCA2 versus without significance and the negative cases stood out, there was no significant statistical difference, but with a tendency to higher frequency of BCRA1. When evaluating breast cancer lines and nuclear grades compared by age, the three nuclear grade groups compared by age showed differences. CONCLUSION: The data obtained show that in the Mexican population the BRCA2 gene has a higher incidence in hereditary cancer, at an age of earlier onset and greater nuclear grade at the time of diagnosis.

A study of susceptibility genes in rare monozygotic twins with generalized aggressive periodontitis / 口腔疾病防治

Objective@#Exploring the effects of susceptibility genes on aggressive periodontitis during its occurrence and development lays a foundation for further research on its genetic pathogenesis.@*Methods@#Medical history and clini⁃ cal indicators were collected from monozygotic twins with generalized aggressive periodontitis. Susceptibility genes were detected by polymerase chain reaction⁃restriction fragment length polymorphisms, and the exon gene components were analyzed by whole⁃exome sequencing. @*Results @#The severity of generalized aggressive periodontitis in the twins was dif⁃ ferent (P < 0.05). Florida diagnosis results showed that the younger sister’ s explored clinical depth (probing depth, PD) and clinical attachment loss (CAL) were higher than those for the elder sister, but her clinical bleeding index (bleeding on probing, BOP) was lower than that of the elder sister. In addition, their responses to periodontal basic treatment were different (P < 0.05). After treatment, the improvement of CAL and decline in BOP were more obvious in the elder sister,and the proportion of different periodontal pocket depths in the elder sister decreased after treatment, while the de⁃ crease was slighter in the younger sister. Genetic tests revealed that the twins had the same genotypes at target suscepti⁃ bility genes (IL⁃1β⁃511, IL⁃1β+3953, TNF⁃α⁃308, FcγR⁃IIIb, VDR, and ER) and differential exon gene components, and that the suspected differential genes, e.g. ZFPM1, PTH2, ZFYVE16, and LY6G6C, might be related to their pheno⁃ typic differences.@* Conclusion@#These monozygotic twins had different phenotypes of generalized aggressive periodonti⁃ tis. Their shared susceptibility genes increased the risk of disease, and their different genetic mutations affected the phe⁃ notype of the disease

Association between KRAS gene mutations and clinicopathological characteristics and prognosis of colorectal cancer patients / 中华消化外科杂志

Objective To investigate the association between KRAS gene mutations and clinicopathological characteristics and prognosis of colorectal cancer (CRC) patients.Methods The retrospective casecontrol study was conducted.The clinicophathological data of 315 patients who underwent radical resection of CRC in the Yangpu Hospital Affiliated to Tongji University between January 2007 and July 2011 were collected.Nextgeneration sequencing was performed to identify KRAS gene mutations from surgical specimens.Observation indicators:(1) detection of KRAS gene;(2) association between KRAS gene mutations and clinicopathological characteristics of CRC patients;(3) follow-up and survival situations;(4) multivariate analysis of KRAS gene mutations in the prognosis of CRC patients.Follow-up using outpatient examination and telephone interview was performed to detect postoperative overall survival up to August 2016.Comparisons of count data were analyzed using the chi-square test.Measurement data with skewed distribution were described as M (interquartile range),and comparison between groups was analyzed using the nonparametric test.The survival rate was calculated using the Kaplan-Meier method,and survival was compared using the Log-rank test.The multivariate analysis was done using the COX regression model.Results (1) Detection of KRAS gene:all the 315 patients finished gene detection of surgical specimens,including 172 in wide-type mutations and 143 in mutant-type mutations (mutations at codon 12 and 13 of KRAS exon 2 and other mutant points were respectively detected in 80,24 and 40 patients,and 1 patient had simultaneous mutations at codon 12 and 13 of KRAS exon 2;missense and nonsense mutations were respectively detected in 141 and 2 patients).The major point mutations were at p.G12D and p.G13D.(2) Association between KRAS gene mutations and clinicophathological characteristics of CRC patients:tumors located in the proximal colon,distal colon and rectum were respectively detected in 34,48,90 patients with wild-type mutation and in 44,27,72 patients with mutant-type mutation,with a statistically significant difference (x2 =0.038,P＜0.05).(3) Follow-up and survival situation:315 patients were followed up for 3-115 months,with a median time of 78 months.The postoperative overall survival rate was 41.0％ in 172 patients with wild-type KRAS mutations,27.4％ in 80 patients with KRAS codon 12 mutations,26.3％ in 24 patients with KRAS codon 13 mutations and 48.2％ in 40 patients with other KRAS mutations,showing a statistically significant difference (x2=0.040,P＜0.05).(4) Multivariate analysis of KRAS gene mutations in the prognosis of CRC patients:the results of multivariate analysis showed that mutations at codon 12 of KRAS exon 2 was an independent factor affecting poor prognosis of CRC patients (Hazard ratio=1.543,95％ confidence interval:1.050-2.265,P＜0.05).Conclusions Most KRAS mutations of CRC patients are at codon 12 and 13 of KRAS exon 2,and the major point mutations are at p.G12D and p.G13D.KRAS gene mutations may be associated with tumor location.Mutations at codon 12 of KRAS exon 2 is an independent factor affecting poor prognosis of CRC patients.

Comparison of influence of radiotherapy, chemotherapy and radiation combined with chemotherapy in the treatment of patients with non-small cell lung cancer on the state of EGFR gene mutation / 中国基层医药

Objective To compare the influence of radiotherapy,chemotherapy and radiation combined with chemotherapy in the treatment of patients with non-small cell lung cancer on the state of EGFR gene mutation.Methods 328 patients with non-small cell lung cancer were selected.On the basis of the condition of the patients,they were treated with radiation therapy,combination treatment with chemotherapy and radiation.And according to the different treatment methods,they were divided into chemotherapy group (112 cases),radiotherapy group (108 cases) and radiation combined with chemotherapy group(108 cases).Before and after treatment,the plasma EGFR mutations situation was detected and analyzed.Results Before treatment,the plasma EGFR mutation rates in the chemotherapy,radiotherapy,radiation combined with chemotherapy group were 34.82％ (39/112),31.48％ (34/108),32.41％ (35/108),which were significantly higher than 20.54％ (23/112),18.52％ (20/108),19.44％ (21/108) after treatment(x2 =5.709,4.840,4.725,all P ＜ 0.05).The frequency of the mutant EGFR gene in the patients after chemotherapy was 20.5％ (23/112),which was significantly lower than 34.8％ (39/112) before chemotherapy,the difference was statistically significant(x2 =5.709,P ＜ 0.05).After radiotherapy,the frequency of the mutant EGFR gene in the patients was 18.5 ％ (20/108),which was significantly lower than 31.5 ％ (34/108) before radiotherapy,the difference was statistically significant(x2 =4.840,P ＜ 0.05).After chemoradiation therapy,the frequency of the mutant EGFR gene in the patients was 19.4％ (21/108),which was significantly lower than 32.4％ (35/108) before chemoradiation therapy,the difference was statistically significant (x2 =4.725,P ＜ 0.05).Conclusion Radiotherapy,chemotherapy and radiation combined with chemotherapy in the treatment of non-small cell lung cancer can affect the state of EGFR gene mutation,which has significant decline.

Current Scenario on Genetic Basis of Infertility- A Review.

Infertility is an emerging major health issue affecting the physical, psychological and social status of the general population across the globe. There are innumerable causes of infertility, viz., ovarian and testicular disorders, advanced maternal age, obesity, chromosomal abnormalities etc. Most of these causes are linked to the genetic disorders. With recent advances in the field of reproductive biology, it has become imperative to have a concise knowledge of the genetic basis of infertility, for better outcome in Assisted Reproductive Techniques (ART).

Survey and research of common thalassemia genotypes in northeast area of Chongqing / 国际检验医学杂志

Objective To understand the gene carrying rate ,gene mutation types and distribution characteristics of thalassemia in the northeast area of Chongqing .Methods 28 633 specimens collected from the patients and individuals with physical examina‐tion in our hospital from January to December 2013 were performed the RBC parameters detection and hemoglobin electrophoresis screening .The specimens with phenotype positive were definitely verified the thalassemia type by using Gap‐PCR and reverse dot blot(RDB) .Results Among 28 633 specimens ,1 358 specimens were finally diagnosed as thalassemia with the thalassemia carrying rate of 4 .74% ,including 589 cases(2 .06% ) of α‐thalassemia and 741 cases (2 .59% ) of β‐thalassemia cases .Among the α‐thalasse‐mia genotypes ,‐αα/‐‐SEA genotype(1 .38% ) was most common ,the next was ‐αα/‐α3 .7 genotype (0 .37% ) and αα/‐α4 .2 genotype (0 .20% ) .Among the β‐thalassemia genotypes ,CD41‐42 genotype (1 .27% ) had the highest constituent ratio ,followed by IVS‐2‐654 genotype(1 .27% ) and CD17 genotype(0 .30% ) .28 cases were found to be the double heterozygote with α‐thalassemia and β‐thalassemia .Conclusion The northeast area of Chongqing is a region with the high incidence rate of thalassemia and complicated heredity .Therefore this research provides the reference information for the prevention of thalassemia ,genetic counseling and prena‐tal diagnosis .

Avanços na etiologia, no diagnóstico e no tratamento da puberdade precoce central / Advances in the etiology, diagnosis and treatment of central precocious puberty

O início da puberdade caracteriza-se pelo aumento de amplitude e frequência dos pulsos do hormônio secretor de gonadotrofinas (GnRH) após um período de relativa supressão hormonal durante a infância. A reemergência da secreção pulsátil do GnRH resulta em aumento na secreção de gonadotrofinas, hormônio luteinizante (LH) e folículo estimulante (FSH), pela hipófise anterior e consequente ativação gonadal. A ativação prematura do eixo hipotálamo-hipófise-gonadal resulta em puberdade precoce dependente de gonadotrofinas, também conhecida como puberdade precoce central (PPC), e se caracteriza pelo desenvolvimento dos caracteres sexuais secundários antes dos 8 anos nas meninas e 9 anos nos meninos. O início do desenvolvimento puberal provém da interação complexa de fatores genéticos, nutricionais, ambientais e socioeconômicos. O diagnóstico clínico da PPC baseia-se em reconhecimento de desenvolvimento puberal progressivo, concentrações púberes de LH em condição basal e/ou após estímulo com GnRH e avanço de idade óssea. A ressonância magnética de encéfalo é útil no estabelecimento de diagnóstico diferencial entre as formas orgânica ou idiopática. Os análogos de GnRH de ação prolongada representam o tratamento de escolha da PPC. O componente genético da PPC foi recentemente fortalecido pela evidência de mutações no gene MKRN3, localizado no braço longo do cromossomo 15, em crianças com PPC familial. Nessa revisão, dados clínicos e terapêuticos da PPC serão amplamente discutidos, visando à atualização e à conduta criteriosa dessa condição clínica de grande relevância na endocrinologia pediátrica.

The onset of puberty is first detected as an increase in the amplitude and frequency of pulses of gonadotropin-releasing hormone (GnRH) after a quiescent period during childhood. The reemergence of pulsatile GnRH secretion leads to increases in the secretion of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by the pituitary gland, and the consequent activation of gonadal function. Early activation of the hypothalamic–pituitary–gonadal axis results in gonadotropin-dependent precocious puberty, also known as central precocious puberty (CPP), which is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Pubertal timing is influenced by complex interactions among genetic, nutritional, environmental, and socioeconomic factors. CPP is diagnosed on the basis of clinical signs of progressive pubertal development before the age of 8 years in girls and 9 years in boys, pubertal basal and/or GnRH-stimulated LH levels, and advanced bone age. Magnetic resonance imaging of the central nervous system is essential for establishing the CPP form as organic or idiopathic. Depot GnRH-analogues represent the first-line of therapy in CPP. Very recently, the genetic component of CPP was demonstrated by the evidence that the deficiency of the MKRN3 gene, located on long arm of chromosome 15, causes familial CPP in humans. In this current review, clinical and therapeutic aspects of the CPP will be discussed, contributing to adequate diagnosis and criterious approach of this relevant condition of pediatric endocrinology.

Effects of different Familial Mediterranean Fever gene mutations and in vitro Colchicine treatment on Peripheral Blood Mononuclear sCells production of IL-6.

Rationale: We wanted to study the effects of Familial Mediterranean Fever (FMF) genetic mutations in Northern Jordan population and in vitro Colchicine treatment on the peripheral blood mononuclear cells (PBMN) production of IL-6 as a marker of disease activity. Methods: - 17 FMF patients and 9 controls were studied. (4 patients had exon 10 mutations only (M680I and V726A), 5 patients had exon 2 mutations (R202Q and E148Q) only and 8 patients with both exon mutations (compound homozygous or heterozygous M694V and R202Q). PBMN cells were incubated with Lipopolysaccharide at 100ng/ml or colchicine 10 ng/ml alone or both. Results: The results showed higher IL-6 levels in the FMF group than control for all treatment modalities, (108.97 vs. 56.49 ng/ml for unstimulated cells) with the highest levels when both exons are involved. Exon 10 mutations were associated with a higher IL-6 level than exon 2 mutations only. Exon 2 mutations alone also were associated with a higher than control IL-6 levels suggesting that it is not a polymorphism phenomenon and is involved in the pathogenesis. In vitro Colchicine treatment caused an increase in the production of IL-6 - although not as high as with LPS - for all groups. Conclusions: Mutations occurring in exon 10 are more significant than mutations occurring in exon 2, although both are contributing to the disease. However colchicine was associated with a paradoxical increase in IL-6 levels. This observation needs confirmation with different colchicine levels in the culture medium and warrants thinking about its exact mechanism of action.

Cáncer de mama asociado a mutaciones genéticas de los BRCA 1 y 2 / Breast cancer associated to BRCA 1 and 2 genetic mutations

Entre el 5 al 10 % de los cánceres de ovario y mama son atribuidos a una transmisión autosómica dominante de mutaciones heredadas en los genes BRCA 1 y BRCA 2. Estos explican el 90 % y el 50 % de los cánceres hereditarios de ovario y mama, respectivamente. Las mujeres que heredan la mutación en el gen BRCA tienen mayor riesgo de cáncer de mama, de ovario y los varones poseedores de dicho gen tienen un riesgo de cáncer de próstata. Las mujeres con la mutación en el gen BRCA 2 también tienen riesgo (aunque menor) de presentar cáncer de mama y de ovario, y en varones hay un riesgo de cáncer de mama. Sin embargo, hay otros síndromes que explican el cáncer hereditario de mama y ovario y otros genes que aún están por descubrirse. Entre estos están el Lynch II, el síndrome Li-Fraumeni, el síndrome de ataxia – telangiectasia, el síndrome de Cowden y el síndrome de Bloom. En la actualidad es posible ofrecer la identificación de estas mutaciones con base en el DNA y en una historia familiar completa, pero la utilidad de la predicción de las pruebas genéticas requiere de una adecuada asesoría para la interpretación de sus resultados.

Between 5 and 10 % of breast and ovarian cancers can be traced to an autosomal dominant mode of inheritance of hereditary mutations in a pair of genes known as BRCA 1 and BRCA 2. They explain 90 % and 50 % of hereditary breast and ovarian cancer, respectively . Women carrying a mutation in the BRCA 1 gene, have a life risk for developing breast cancer and for ovarian cancer, a higher risk of colon cancer and men have a high risk of prostatic cancer. Women having the BRCA 2 gene mutation also have the same risk to develop breast cancer but the ovarian cancer is lower (10 % at 70 years) and is characterized for a risk of 6 % of breast cancer in men. Besides there are other known causes of these hereditary syndromes, other implicated genes still to be discovered. The more renoume syndromes are Lynch II, Li-Fraumeni, Ataxia – Telangiectasia, Cowden and Bloom syndromes, etc. Currently, it is possible to convey detection of carriers of these mutations based on DNA and a complete family history, but the useful prediction of genetic tests requires a formal counseling to interpret the results.

Anomalías del desarrollo del segmento anterior / Anomalies in the development of the anterior segment

Las disgenesias del segmento anterior forman parte de un grupo de anomalías del desarrollo ocular que comparten características clínicas y se acompañan en su gran mayoría de glaucoma. En esta revisión se empleó la clasificación usada por Taylor, que las divide en anomalías originadas en las células de la cresta neural, anomalías ectodérmicas y anomalías de origen global, se describen sus características clínicas, tratamiento y alteraciones genéticas. Debido a la variabilidad de cuadros clínicos, se hace más necesaria la identificación de los genes en el desarrollo del segmento anterior que permite la clasificación de estas disgenesias, según la mutación genética subyacente.

The anterior segment dysgeneses are part of a group of anomalies of the ocular development that share clinical characteristics and are mostly accompanied by glaucoma. This article used Taylor´s classification, which divides them into anomalies originated in the the neural crest cells , ectodermic anomalies and anomalies of global origin, describing their clinical characteristics, treatment and genetic alterations. Taking into account the diversity of clinical findings, it is increasingly important to identify gens in the development of the anterior segment which allow the classification of these dysgeneses according to the underlying genetic mutation.

Síndromes nefróticos congénitos y hereditarios / Congenital and heritable nephrotic syndromes

En los últimos años se han identificado muchos síndromes nefróticos familiares y esporádicos que no responden a los tratamientos habituales (esteroides e inmunosupresores), evolucionan con relativa rapidez a la insuficiencia renal crónica y se producen por mutaciones genéticas. La mayoría de los síndromes nefróticos que se trasmiten genéticamente y que pueden ser congénitos, presentarse en el primer año de la vida, o en el niño mayor, son atribuidos a mutaciones en los genes NPHS1, NPHS2, WT1 y LAMB2. Otros síndromes nefróticos producidos por mutaciones genéticas pueden no manifestarse hasta la adultez. El objetivo fundamental de esta revisión fue llamar la atención sobre los síndromes nefróticos producidos por mutaciones genéticas en los que no sólo no se obtienen resultados con los tratamientos inmunosupresores, si no en los que dichos tratamientos pueden ser perjudiciales para el paciente

In past years many familial and sporadic nephrotic syndromes refractory to usual treatments (steroids and immunosuppressives), evolve quickly to a chronic renal failure produced by genetic mutations. Most of nephrotic syndromes genetically transmitted and that may be congenital, present in the first year of life or in the older child, are attributable to NPHS1, NPHS2, WT1 and KLAMB2 gen mutations. Other nephrotic syndromes produced by genetic mutations may not appear until adulthood. The main objective of present review was to alert on the nephrotic syndromes produced by genetic mutations without response to immunosuppressive treatments, but on those in which such treatment may be dangerous for patient

Genetic Mutations of HBV Core Region / 中华医院感染学杂志

OBJECTIVE To study the mutation profiles of hepatitis B virus(HBV) in the core regions.METHODS Based on the sequence alignment of all HBV genotypes,specific primers targeting all HBV genotypes were designed to amplify the core region of HBV followed by sequence analysis on the sequencing data available.RESULTS Among the 34 cases,23 cases showed mutations in the core region.According to the mutation profiles,the most common mutations were the A1762T(50.0%) and G1764A(52.9%) in the basic core promoter(BCP) regions,and it always showed as double mutations.The L60V in core gene regions was the secondary common mutations(17.6%).Among all patients,there were 18,6 and 10 cases showed mutations in BCP,pre-core,and core gene regions,respectively.The most common mutations in BCP,pre-core,and core gene regions were the double mutations at A1762T and G1764A(94.7%),G1896A(83.3%),and L60V(50.0%),respectively.CONCLUSIONS The most common mutations in the core region of HBV are the double mutations at A1762T and G1764A.Analysis on the mutation profiles of HBV core regions might be helpful for the prognosis and prediction of HBV infections.