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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 37-40, 2020 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-31922593

RESUMO

OBJECTIVE: To determine the frequency, common chromosomal karyotypes and breakpoints, and involved regions among carriers of reciprocal translocations from Henan Province, and to explore the influence of common breakpoint regions on pregnancy and fetal development. METHODS: For 586 carriers of reciprocal translocations, the above features were retrospectively analyzed. RESULTS: The 586 reciprocal translocations were identified among 62 477 subjects, which yielded a frequency of 0.94%. Among these, 572 (0.92%) had abnormal fertility, and 14 (0.02%) had a history of abnormal fetal development. Statistical analysis showed that chromosomes 1, 4, 7 and 11 were most frequently involved, with t(11;22)(q25;q13) being the most common type of translocation. In total 437 breakpoint regions were identified, with 11q23, 22q13 and 1p36 being most frequently involved, which resulted in infertility, abortion, embryo death, congenital malformation, development delay, mental retardation or a normal phenotype. CONCLUSION: Above results indicated a 0.92% carrier rate for reciprocal chromosomal translocations in Henan. The location of breakpoint regions may affect the pregnancy and/or fetal development. Discovery of such regions may enable more accurate genetic, reproductive and developmental counseling for carriers, and provide reference for delineation of function and pathogenetic mechanism of the relevant genes.


Assuntos
Pontos de Quebra do Cromossomo , Translocação Genética , Feminino , Heterozigoto , Humanos , Cariótipo , Cariotipagem , Gravidez , Estudos Retrospectivos , Translocação Genética/genética
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 41-43, 2020 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-31922594

RESUMO

OBJECTIVE: To explore the genetic basis of a patient featuring global developmental delay, intellectual disability, cleft palate, seizures and hypotonia. METHODS: Clinical examination and laboratory tests were carried out. Peripheral blood samples were obtained from the patient and his parents. Whole genomic DNA was extracted and subjected to next generation sequencing. Candidate variation was analyzed by using bioinformatic software and validated by Sanger sequencing. RESULTS: The proband was found to carry a heterozygous c.2117T>C (p.Leu706Pro) variant of the NEDD4L gene, which was a de novo variant validated by Sanger sequencing and predicted to be likely pathogenic according to the American College of Medical Genetics Guidelines. CONCLUSION: The heterozygous variant of c.2117T>C (p.Leu706Pro) of the NEDD4L gene probably underlies the disorders in the patient.


Assuntos
Ubiquitina-Proteína Ligases Nedd4 , Heterotopia Nodular Periventricular , Testes Genéticos , Heterozigoto , Humanos , Deficiência Intelectual/etiologia , Deficiência Intelectual/genética , Masculino , Mutação , Ubiquitina-Proteína Ligases Nedd4/genética , Heterotopia Nodular Periventricular/complicações , Heterotopia Nodular Periventricular/genética
3.
J Clin Pathol ; 73(1): 7-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31422373

RESUMO

AIMS: Hereditary protein S (PS) deficiency is one of the natural anticoagulant deficiencies causing thrombophilia. We herein described a young male with recurrent deep venous thrombosis, who was diagnosed as type I PS deficiency with compound heterozygous mutations of PROS1 gene. We aimed to analyse the relationship between the genotype and phenotype detection and investigate the pathological mechanisms of PROS1 mutations causing PS deficiency. METHODS: Genetic analysis of PROS1 gene was carried out by direct sequencing. Thrombin generation potential and the inhibition function of thrombin generation by plasma PS were detected by thrombin generation test (TGT). The mRNA transcription level of mutant PS in vitro was measured by real-time PCR, while the protein level was evaluated by western blot and ELISA. Cellular distribution of the protein was further analysed by immunofluorescence. RESULTS: Compound heterozygous mutations (PROS1 c.1551_1552delinsG, p.Thr518Argfs*39 and PROS1 c.1681C>T, p.Arg561Trp) were identified in the propositus, and the former one was a novel small indel mutation. TGT results showed impaired inhibition of thrombin generation with the addition of activated protein C in his parents with certain heterozygous mutations. In vitro expression study, p.Thr518Argfs*39 mutant produced truncated protein retained in the cytoplasm, while p.Arg561Trp mutant partially affected the secretion of PS. Both mutations are located in C-terminal sex hormone-binding globulin (SHBG)-like domain of PS. CONCLUSIONS: Compound heterozygous mutations identified in the study have strong detrimental effect, causing severe type I PS deficiency in the propositus. SHBG-like domain of PS might play an important role in PS secretion system.


Assuntos
Coagulação Sanguínea/genética , Proteínas Sanguíneas/genética , Heterozigoto , Mutação , Deficiência de Proteína S/genética , Trombose Venosa/genética , Adulto , Proteínas Sanguíneas/metabolismo , Feminino , Predisposição Genética para Doença , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Deficiência de Proteína S/sangue , Deficiência de Proteína S/diagnóstico , Recidiva , Via Secretória , Índice de Gravidade de Doença , Trombina/metabolismo , Trombose Venosa/sangue , Trombose Venosa/diagnóstico
4.
Angiol Sosud Khir ; 25(4): 28-33, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31855198

RESUMO

BACKGROUND: Diabetes mellitus a commonly encountered pathology in the whole world and has a tendency towards steady growth of morbidity and development of vascular complications. The presence of haemostatic disorders and genetic susceptibility to thrombosis in patients with diabetes mellitus increases the risk for the development of thrombotic complications. AIM: The purpose of the study was to determine the incidence rate of thrombophilic conditions (TC) and thrombosis-associated gene carrier status (TAGCS) in patients suffering from neuroischaemic form of diabetic foot. PATIENTS AND METHODS: The study enrolled a total of 38 patients undergoing treatment at the Department of Vascular Surgery for critical ischaemia of lower limbs combined with diabetes mellitus during the period from 2016 to 2018. There were 29 (76.3%) men and 9 (23.7%) women. The mean age amounted to 58.9±7.3 years. The diagnosis of TC and TAGCS was made based on the study for the presence of the markers of antiphospholipid syndrome, level of homocysteine and antithrombin III, proteins C and S, as well as comprehensive genetic study in order to reveal gene polymorphisms (prothrombin, Leiden mutation, MTHFR gene, MTR gene and others). Based on the obtained findings we calculated the incidence rate of TC and TAGCS, as well as their combinations in the examined patients. RESULTS: In the studied group of patients we revealed various incidence of TC and TAGCS, and, most importantly, that of a combination of these conditions. All cases of thrombophilias were combined with TAGCS. Hyperhomocysteinemia was most commonly combined with the MTRR 66 A>G gene mutation, the presence of lupus anticoagulant - with PAI-1 675 5G>4G, whereas thrombophilic conditions - with MTRR 66 A>G and PAI-I - 675 5G>4G. Two patients were found to be carriers of the factor V Leiden mutation. CONCLUSION: The examined patients were diagnosed as having TC or TAGCS, as well as their combinations in one form or another, thus increasing the risk for the development of thromboses and embolisms in such patients.


Assuntos
Complicações do Diabetes/complicações , Pé Diabético/etiologia , Tromboembolia/etiologia , Trombofilia/complicações , Idoso , Complicações do Diabetes/genética , Pé Diabético/genética , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Tromboembolia/genética , Trombofilia/genética
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1100-1103, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703135

RESUMO

OBJECTIVE: To analyze the phenotype and F5 gene variant in a pedigree affected with hereditary coagulation factor V (FV) deficiency. METHODS: All of the exons, flanking sequences, and 5' and 3' untranslated regions of the F5 gene were subjected to PCR and direct sequencing. Suspected variant sites were confirmed by clone sequencing. Influence of the variants was predicted by using software including ClustalX and Mutation Taster. RESULTS: The prothrombin time (PT) and activated partial thromboplastin time (APTT) of the proband were prolonged to 20.3 s and 59.2 s, respectively, while FV activity (FV:C) and FV antigen (FV:Ag) were reduced by 13% and 17%, respectively. The FV:C and FV:Ag of his father, sister and daughter were decreased to 35%, 37%, 29% and 42%, 46%, 35%, respectively. The proband was found to carry a heterozygous c.2851delT variant in exon 13 of the F5 gene, which caused a frameshift and resulted in a truncated protein (p.Ser923LeufsX8). In addition, a heterozygous c.1538G to A (p.Arg485Lys) variant was found in exon 10. The father, sister and daughter of the proband all carried the p.Ser923LeufsX8 variant, while his mother and son carried the heterozygous p.Arg485Lys polymorphism. His younger brother and wife were of the wild type. Bioinformatic analysis showed that p.Ser923 was highly conserved across various species. Mutation Taster scored 1.00 for the p.Ser923LeufsX8 variant, and the result has predicted a corresponding disease. CONCLUSION: A heterozygous deletional mutation c.2851delT in exon 13 of the F5 gene and a heterozygous c.1538G to A polymorphism harbored by the proband may be associated with the decreased FV level in this pedigree.


Assuntos
Deficiência do Fator V/genética , Fator V/genética , Deleção de Genes , Feminino , Testes Genéticos , Heterozigoto , Humanos , Masculino , Mutação , Linhagem , Fenótipo
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1115-1119, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703139

RESUMO

OBJECTIVE: To explore the genetic basis for a boy with mental retardation. METHODS: Clinical data and peripheral blood samples of the family were collected. Potential variants were screened by using a panel for genes associated with intellectual impairment. Suspected variants were verified by PCR and Sanger sequencing. RESULTS: The child presented with mental retardation, language delay and poor self-care. Imaging analysis showed widening of brain fissures and subarachnoid space, and dysplasia of corpus callosum. Three novel heterozygous variants, namely c.1705T to C (p.S569P), c.1708dupC (p.R570Pfs*80) and c.2273delA (p.N758Tfs*22), were identified in the TRAPPC9 gene. The mother of the proband has carried the c.1708dupC (p.R570Pfs*80) and c.1705T to C (p.S569P) variants, while his father has carried the c.2273delA (p.N758Tfs*22) variant. CONCLUSION: The compound heterozygous variants of the TRAPPC9 gene probably underlie the disease in this family. Considering the clinical and genetic heterogeneity of mental retardation, genetic testing is essential for attaining diagnosis for patients with the relevant phenotype.


Assuntos
Proteínas de Transporte/genética , Deficiência Intelectual/genética , Criança , Testes Genéticos , Heterozigoto , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Mutação , Fenótipo
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1130-1132, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703143

RESUMO

OBJECTIVE: To analyze the hematological characteristics of a patient with Hb Ottawa in conjunction with ß -thalassemia. METHODS: Peripheral blood samples from the proband and her parents were collected and subjected to red blood cell analysis and hemoglobin electrophoresis. Genotypes of α - and ß -globin genes were also analyzed. RESULTS: The proband and her mother were both heterozygotes for Hb Ottawa and ß -thalassemia variant IVS II-654, and presented with typical ß -thalassemia trait featuring hypochromic microcytic anemia. An abnormal hemoglobin band was detected upon electrophoresis. CONCLUSION: Co-existence of Hb Ottawa and ß -thalassemia may not aggravate the phenotype.


Assuntos
Hemoglobinas Anormais/genética , Talassemia beta/genética , Feminino , Testes Genéticos , Heterozigoto , Humanos , alfa-Globinas/genética , Globinas beta/genética
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 1002-1005, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598946

RESUMO

OBJECTIVE: To detect potential variation in an ethnic Han Chinese family affected with late-onset lipid storage myopathy. METHODS: Next generation sequencing (NGS) was used to screen disease-related genes in the proband. Suspected mutation was validated with PCR and Sanger sequencing in two patients, their father, and 100 healthy controls. RESULTS: Heterozygous c.770A>G (p.Tyr257Cys) and c.1395dupT (p.Gly466Tryfs) mutation were detected in the two patients. Their father was found to be heterozygous for the c.770A>G (p.Tyr257Cys) mutation, while the c.1395dupT (p.Gly466Tryfs) variation was not reported previously and not found among the healthy controls. CONCLUSION: Mutations of the ETFDH gene probably underlie the pathogenesis in this family. The novel c.1395dupT (p.Gly466Tryfs) has enriched the mutation spectrum of EDFDH gene.


Assuntos
Flavoproteínas Transferidoras de Elétrons/genética , Proteínas com Ferro-Enxofre/genética , Erros Inatos do Metabolismo Lipídico/genética , Distrofias Musculares/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Grupo com Ancestrais do Continente Asiático , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 1006-1009, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598947

RESUMO

OBJECTIVE: To detect potential mutations of the coagulation factor Ⅶ (F7) gene in a pedigree affected with hereditary FⅦ deficiency and explore its molecular pathogenesis. METHODS: The FⅦ antigen (FⅦ:Ag) was analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Prothrombin time (PT), FⅦ activity (FⅦ:C) and other coagulant parameters were quantified with an one-stage clotting assay. The F7 gene was amplified by PCR and sequenced. Mutational sites were confirmed by reverse sequencing. Impact of amino acid substitution was assessed using SIFT and PolyPhen-2 software. Structure of the mutant protein was analyzed using Swiss-pdb Viewer software based on the three-dimensional structure in the Protein Data Bank. RESULTS: The propositus had prolonged PT (36.3 s), with FⅦ:C and FⅦ:Ag significantly reduced to 2% and 44%, respectively. Her father, mother, younger sister and daughter had slightly prolonged PT and reduced FⅦ:C (86%-120%). The FⅦ:Ag of her father and younger sister were also reduced. DNA sequencing revealed that the propositus has carried compound heterozygous mutations (Lys341Glu and IVS6-1G>A) of the F7 gene. Her father and younger sister were heterozygous for the IVS6-1G>A mutation, while her mother and daughter were heterozygous for the Lys341Glu mutation. Bioinformatics analysis indicated that Lys341Glu mutation may affect the stability and function of the FⅦ protein. CONCLUSION: The Lys341Glu and IVS6-1G>A mutations probably underlie the reduced activity of FⅦ in this pedigree.


Assuntos
Deficiência do Fator VII/genética , Fator VII/genética , Feminino , Testes Genéticos , Heterozigoto , Humanos , Masculino , Mutação , Linhagem
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 1022-1024, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598951

RESUMO

OBJECTIVE: To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF). METHODS: Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The fetus was found to carry compound heterozygous variants c.1440+1G>A and c.925G>T of the NPHS1 gene, which were respectively inherited from its mother and father. CONCLUSION: Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.


Assuntos
Síndrome Nefrótica/congênito , Síndrome Nefrótica/diagnóstico , Feminino , Feto , Finlândia , Heterozigoto , Humanos , Proteínas de Membrana/genética , Gravidez , Diagnóstico Pré-Natal
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1592-1595, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607317

RESUMO

OBJECTIVE: To investigate the gene-carrying rate and genetic types of thalassemia among the couples of child-bearing age in Ding'an, Hainan province. METHODS: A total of 1742 couples at child bearing age in the region were screened for thalassemia by detecting the mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV). If the sample data of either spouse of couples was tested as MCV<82 fl and /or MCH<27 pg, both samples of the couple would be further assayed by hemoglobin electrophoresis. Those samples of HbA2 2.5 % or HbA2>3.5 % were judged as positive in the preliminary screening, then subjected to genetic diagnosis of thalassemia. RESULTS: 478 cases out of 1 742 couples of child bearing age were diagnosed as thalassemia gene mutation, and the gene-carrying rate was 13.72 %. In those carriers, 42 couples were diagnosed with the same type of thalassemia, accounting for 3.67 %. The gene-carrying rate of α-thalassemia, ß-thalassemia and αß-thalassemia was 9.56%, 3.10% and 1.06 % respectively. CONCLUSION: The Ding'an area in Hainan Province is an area with high incidence of thalassemia, and the main genotype is α-thalassemia, showing a distribution of local characteristics. The government should make efferts to popularise the screening for thalassemia, so as to effectively prevent the birth of children with thalassemia major.


Assuntos
Testes Genéticos , Talassemia alfa , Talassemia beta , Índices de Eritrócitos , Heterozigoto , Humanos
12.
Int Heart J ; 60(5): 1113-1122, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484864

RESUMO

Occurring in about 1% of all live births, congenital heart defects (CHDs) represent the most frequent type of developmental abnormality and account for remarkably increased infant morbidity and mortality. Aggregating studies demonstrate that genetic components have a key role in the occurrence of CHDs. Nevertheless, due to pronounced genetic heterogeneity, the genetic causes of CHDs remain unclear in most patients. In this research, 114 unrelated patients affected with CHDs and 218 unrelated individuals without CHDs served as controls were recruited. The coding regions and splicing donors/acceptors of the ISL1 gene, which codes for a transcription factor required for proper cardiovascular development, were screened for mutations by sequencing in all study participants. The functional characteristics of an identified ISL1 mutation were delineated with a dual-luciferase reporter assay system. As a result, a new heterozygous ISL1 mutation, NM_002202.2: c.225C>G; p. (Tyr75*), was discovered in an index patient with double outlet right ventricle and ventricular septal defect. Analysis of the proband's family unveiled that the mutation co-segregated with the CHD phenotype. The nonsense mutation was absent in the 436 control chromosomes. Biological analysis showed that the mutant ISL1 protein had no transcriptional activity. Furthermore, the mutation nullified the synergistic activation between ISL1 and TBX20, another CHD-associated transcription factor. This research for the first time links an ISL1 loss-of-function mutation to double outlet right ventricle in humans, which adds insight to the molecular pathogenesis underpinning CHDs, suggesting potential implications for timely personalized management of CHD patients.


Assuntos
Dupla Via de Saída do Ventrículo Direito/genética , Genes Reporter/genética , Predisposição Genética para Doença/epidemiologia , Proteínas com Homeodomínio LIM/genética , Mutação com Perda de Função/genética , Fatores de Transcrição/genética , Estudos de Casos e Controles , Causalidade , Pré-Escolar , China/epidemiologia , Dupla Via de Saída do Ventrículo Direito/diagnóstico por imagem , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/genética , Heterozigoto , Hospitais Universitários , Humanos , Incidência , Lactente , Masculino , Mutação , Linhagem , Prognóstico , Estudos Retrospectivos , Medição de Risco
13.
BMC Med Genet ; 20(1): 152, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488071

RESUMO

BACKGROUND: Consanguine families display a high degree of homozygosity which increases the risk of family members suffering from autosomal recessive disorders. Thus, homozygous mutations in monogenic obesity genes may be a more frequent cause of childhood obesity in a consanguineous population. METHODS: We identified 23 probands from 23 Pakistani families displaying autosomal recessive obesity. We have previously excluded mutations in MC4R, LEP and LEPR in all probands. Using a chip-based, target-region capture array, 31 genes involved in monogenic forms of obesity, were screened in all probands. RESULTS: We identified 31 rare non-synonymous possibly pathogenic variants (28 missense and three nonsense) within the 31 selected genes. All variants were heterozygous, thus no homozygous pathogenic variants were found. Two of the rare heterozygous nonsense variants identified (p.R75X and p.R481X) were found in BBS9 within one proband, suggesting that obesity is caused by compound heterozygosity. Sequencing of the parents supported the compound heterozygous nature of obesity as each parent was carrying one of the variants. Subsequent clinical investigation strongly indicated that the proband had Bardet-Biedl syndrome. CONCLUSIONS: Mutation screening in 31 genes among probands with severe early-onset obesity from Pakistani families did not reveal the presence of homozygous obesity causing variants. However, a compound heterozygote carrier of BBS9 mutations was identified, indicating that compound heterozygosity must not be overlooked when investigating the genetic etiology of severe childhood obesity in populations with a high degree of consanguinity.


Assuntos
Consanguinidade , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Obesidade Pediátrica/genética , Síndrome de Bardet-Biedl/genética , Índice de Massa Corporal , Pré-Escolar , Códon sem Sentido , Feminino , Genótipo , Heterozigoto , Homozigoto , Humanos , Leptina/genética , Masculino , Mutação , Paquistão , Obesidade Pediátrica/fisiopatologia , Linhagem , Receptor Tipo 4 de Melanocortina/genética , Receptores para Leptina/genética
14.
Gynecol Oncol ; 155(2): 270-274, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31500890

RESUMO

OBJECTIVE: To compare the survival experience of women with a BRCA1 mutation who enrolled in an ovarian cancer screening program with that of women who opted for preventive oophorectomy. METHODS: We followed 1964 women with a BRCA1 mutation and two ovaries intact in a prospective study. No women had ovarian cancer or had a bilateral oophorectomy prior to study initiation. There were 1814 women in the cohort who had at least one screening ultrasound. They were followed from the date of first ultrasound until the date of preventive oophorectomy, death or last follow-up. There were 659 women in the cohort who had preventive oophorectomy. They were followed from the date of preventive oophorectomy until death or last follow-up. RESULTS: Among the 1196 women who had one or more ultrasound examinations and no oophorectomy, there were 73 incident cancers detected and 27 deaths from ovarian/fallopian cancer. The ten year cumulative risk of death was 2.0%. Among the 659 women who had a preventive oophorectomy there were 12 incident cancers (9 detected at oophorectomy and 3 in the follow up period) and two deaths from ovarian cancer. The ten year cumulative risk of death was 0.5%. The hazard ratio for oophorectomy versus ultrasound was 0.23 (95% CI: 0.05 to 0.97; p = 0.05). CONCLUSION: The survival of women diagnosed with ovarian cancer enrolled in an ultrasound screening program is relatively poor and screening is not a viable alternative to preventive oophorectomy.


Assuntos
Neoplasias Ovarianas/mortalidade , Ovariectomia/mortalidade , Adulto , Idoso , Detecção Precoce de Câncer , Feminino , Genes BRCA1/fisiologia , Heterozigoto , Humanos , Programas de Rastreamento/mortalidade , Pessoa de Meia-Idade , Mutação/genética , Neoplasias Ovarianas/prevenção & controle , Polônia/epidemiologia , Estudos Prospectivos , Ultrassonografia , Adulto Jovem
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 866-869, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515777

RESUMO

OBJECTIVE: To determine the CGG repeat number and methylation status of FMR1 gene for fetuses whose mothers have carried a FMR1 mutation. METHODS: For 30 pregnant women, the fetal CGG repeat number was determined with a GC-rich PCR system by using chorionic villus, amniotic fluid or umbilical blood samples. The methylation status of the FMR1 gene was confirmed with Southern blotting. RESULTS: In total 30 prenatal diagnoses were performed for 29 carriers of FMR1 gene mutations and 1 with FMR1 gene deletion mosaicism. Three fetuses were found to carry premutations, 9 were with full mutations and 1 with mosaicism of premutation and full mutations. Eighteen fetuses were normal. CONCLUSION: Considering the genetic complexity of Fragile X syndrome (FXS), single method may not suffice accurate determination of their genetic status. The pitfalls and technical limitations of protocols requires adoption of personalized strategy for its prenatal diagnosis.


Assuntos
Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/diagnóstico , Diagnóstico Pré-Natal , Feminino , Heterozigoto , Humanos , Mutação , Gravidez
17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 882-885, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515781

RESUMO

OBJECTIVE: To screen for potential variants of GCDH gene in 3 patients clinically diagnosed as glutaric aciduria type Ⅰ. METHODS: GCDH gene variants was detected by Sanger sequencing among the three children and their family members. RESULTS: Sanger sequencing showed that patient 1 carried compound heterozygosity variants of c.532G>A (p.Gly178Arg) and c.655G>A (p.Ala219Thr) of the GCDH gene, while his father and mother respectively carried heterozygous c.532G>A(p.Gly178Arg) and c.655G>A (p.Ala219Thr) variants. Patient 2 carried c.532G>A (p.Gly178Arg) and a novel c.1060G>T (p.Gly354Cys) compound heterozygous variant, while his father and mother respectively carried heterozygous c.532G>A (p.Gly178Arg) and c.1060G>T (p.Gly354Cys) variant. Patient 3 carried homozygous c.532G>A (p.Gly178Arg) variant of the GCDH gene, for which both of his parents were heterozygous carriers. CONCLUSION: The GCDH gene variant probably underlie the glutaric aciduria type Ⅰ among the 3 patients. Identifcation of the novel variant has enriched the spectrum of GCDH gene variants.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Encefalopatias Metabólicas/genética , Glutaril-CoA Desidrogenase/deficiência , Feminino , Glutaril-CoA Desidrogenase/genética , Heterozigoto , Humanos , Masculino
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 893-896, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515784

RESUMO

OBJECTIVE: To analyze genetic variant in a pedigree affected with congenital high myopia. METHODS: Whole exome sequencing (WES) was carried out for the proband. Suspected variation was verified with Sanger sequencing. The pedigree was also subjected to co-segregation analysis. RESULTS: WES has identified a novel splice site heterozygous variant (c.2556+1G>A) in the COL11A1 gene in the proband. Co-segregation analysis of the pedigree showed that the affected mother and two daughters of the proband have carried the same variant(c.2556+1G>A), while his unaffected father and sister did not. Based on the ACMG Standards and Guidelines for the Interpretation of Sequence Variants, the variant was classified as "likely pathogenic" (PVS1+PM2). CONCLUSION: A novel splice variant (c.2556+1G>A) of the COL11A1 gene has been identified in a pedigree affected with congenital high myopia, which probably underlies the disease.


Assuntos
Colágeno Tipo XI/genética , Miopia/genética , Testes Genéticos , Heterozigoto , Humanos , Linhagem , Sequenciamento Completo do Exoma
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 910-913, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515788

RESUMO

OBJECTIVE: To explore the genetic basis for an infant featuring developmental delay, hand deformity and hypertonia of extremities. METHODS: Clinical data and peripheral blood samples of the proband and her parents were collected. Following DNA extraction, potential mutations were screened on an Ion PGM platform using a gene panel. Suspected mutation was verified by PCR and Sanger sequencing. RESULTS: A novel heterozygous nonsense mutation, c.2521C>T(p.R841X), was identified in the NIPBL gene. The mutation may cause premature termination of translation of the adhesion protein loading factor at 841st amino acids. The same mutation was not found in her parents and 931 healthy controls, and was absent from public databases including ExAC and 1000G. Bioinformatic analysis suggested the mutation to be disease causing. CONCLUSION: The c.2521C>T (p.R841X) mutation of the NIPBL gene probably underlies the Cornelia De Lange syndrome in the infant. Prenatal diagnosis may be provided to this family upon their subsequent pregnancy.


Assuntos
Síndrome de Lange/genética , Diagnóstico Pré-Natal , Proteínas/genética , Proteínas de Ciclo Celular , Síndrome de Lange/diagnóstico , Feminino , Heterozigoto , Humanos , Lactente , Mutação , Gravidez
20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 918-921, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515790

RESUMO

OBJECTIVE: To explore phenotypic and mutational characteristics of a pedigree affected with autosomal dominant Charcot-Marie-Tooth disease (CMT) and nephropathy. METHODS: Clinical data of the proband and his family members was collected. Electrophysiology, renal biopsy and next-generation sequencing were carried out for the proband. RESULTS: The proband presented with distal lower limb weakness and proteinuria in childhood. His mother and brother had similar symptoms. Electrophysiological test of the proband revealed demyelination and axonal changes in both motor and sensory nerves. Renal biopsy suggested focal segmental glomerulosclerosis. Genetic testing revealed a heterozygous c.341G>A (p.G114D) mutation in exon 2 of the INF2 gene. CONCLUSION: The phenotypic feature of the pedigree is autosomal dominant intermediate CMT and focal segmental glomerulosclerosis, which may be attributed to the c.341G>A mutation of the INF2 gene.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Glomerulosclerose Segmentar e Focal/genética , Proteínas dos Microfilamentos/genética , Doença de Charcot-Marie-Tooth/complicações , Criança , Feminino , Glomerulosclerose Segmentar e Focal/complicações , Heterozigoto , Humanos , Masculino , Mutação , Linhagem
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