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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 17-20, 2020 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-31922588

RESUMO

OBJECTIVE: To explore the genetic basis of a pedigree affected with hereditary spherocytosis. METHODS: Peripheral blood samples were collected from 17 members of the pedigree. Genomic DNA of the proband was subjected to next generation sequencing. Candidate variant was validated by co-segregation analysis. pCAS2(c.5798+1G) and pCAS2(c.5798+1A) plasmids were constructed by homologous recombination and transfected into 293T cells. Reverse transcription PCR, TA cloning and Sanger sequencing were used to analyze the effect of candidate variant on splicing. Meanwhile, peripheral blood RNAs were extracted to analyze the effect of candidate variant on splicing in vivo. RESULTS: The proband was found to carry a c.5798+1G>A variant of the SPTB gene. The variant has co-segregated with the phenotype in the pedigree. In vitro and in vivo splicing experiments confirmed that the mutation has significantly affected the splicing, resulting in shift of reading frame and produced a premature termination codon. CONCLUSION: The novel c.5798+1G>A variant of the SPTB gene probably underlies the pathogenesis of hereditary spherocytosis in this pedigree.


Assuntos
Espectrina , Esferocitose Hereditária , Códon sem Sentido/genética , Variação Genética , Células HEK293 , Humanos , Mutação/genética , Linhagem , Plasmídeos , Processamento de RNA , Espectrina/genética , Esferocitose Hereditária/genética , Transfecção
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 25-27, 2020 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-31922590

RESUMO

OBJECTIVE: To explore the genetic etiology of a pedigree affected with Norrie disease. METHODS: Four individuals from the core family of the proband were subjected to whole exome sequencing in order to identify the pathological variant. Sanger sequencing was used to verify the finding among 7 additional members from the pedigree. RESULTS: The proband and other 3 male patients have all carried a hemizygote c.361C>T (p.Arg121Trp) missense variant of the NDP gene, for which his mother, grandmother and two younger female cousins were heterozygous carriers. The same variant was not detected among unaffected males. Above results conformed to a X-linked recessive pattern of inheritance. CONCLUSION: The missense variant c.361C>T of the NDP gene probably underlies the Norrie disease in this pedigree.


Assuntos
Cegueira/congênito , Proteínas do Olho , Doenças Genéticas Ligadas ao Cromossomo X , Proteínas do Tecido Nervoso , Doenças do Sistema Nervoso , Degeneração Retiniana , Espasmos Infantis , Cegueira/genética , Proteínas do Olho/genética , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Masculino , Proteínas do Tecido Nervoso/genética , Doenças do Sistema Nervoso/genética , Linhagem , Degeneração Retiniana/genética , Espasmos Infantis/genética
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 60-63, 2020 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-31922599

RESUMO

OBJECTIVE: To explore the molecular basis for a pedigree affected with May-Hegglin anomaly (MHA). METHODS: Peripheral blood samples were collected and subjected to DNA extraction. Exons 1, 10, 16, 24, 25, 26, 30, 31, 33, 38 and 40 and flanking sequences of the MYH9 gene were subjected to PCR amplification and Sanger sequencing. Changes in protein expression were determined by an indirect immunofluorescence assay. Platelet aggregation function of the proband was assessed by thromboelastogram. RESULTS: The proband and his second son both carried a heterozygous 5521G>A (GAG to AAG) missense variant in exon 38 of the MYH9 gene, leading to p.Glu1841Lys substitution at position 1841 of amino acid sequence. Immunofluorescence showed inclusions containing NMMHC-II A. Thromboelastogram suggested enhanced platelet aggregation function of the proband. CONCLUSION: The c.5521G>A variant of MYH9 gene has co-segregated with the phenotype of MHA in this pedigree. To assess the aggregation function of platelet by thromboelastogram can predict the risk of bleeding in MHA patients.


Assuntos
Perda Auditiva Neurossensorial , Cadeias Pesadas de Miosina , Trombocitopenia/congênito , Perda Auditiva Neurossensorial/genética , Humanos , Masculino , Mutação , Cadeias Pesadas de Miosina/genética , Linhagem , Trombocitopenia/genética
4.
Gene ; 725: 144164, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31639430

RESUMO

Bardet-Biedl syndrome (BBS) is a clinically and genetically heterogeneous ciliopathy with several clinical features including retinitis pigmentosa, obesity, kidney dysfunction, postaxial polydactyly, behavioral dysfunction and hypogonadism with wide spectrum of additional features. With multiple phenotypes and heterogeneous distribution, it is unlikely that BBS is caused by single gene defect. We have performed clinical and genetic diagnosis of two individuals from an Indian family with classical BBS symptoms. Whole exome sequencing identified homozygous missense mutation in BBS10 gene, hemizygous missense AR and homozygous missense PDE6B mutations in the proband and affected sibling with BBS. Identification of BBS10 mutation along with AR and PDE6B gene mutation will expand the genetic and phenotypic spectrum in individuals with BBS.


Assuntos
Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/metabolismo , Chaperoninas/genética , Chaperoninas/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 6/genética , Análise Mutacional de DNA , Estudos de Associação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação/genética , Linhagem , Fenótipo , Receptores Androgênicos/genética , Retinite Pigmentosa/genética , Sequenciamento Completo do Exoma/métodos , Adulto Jovem
5.
Medicine (Baltimore) ; 98(50): e18253, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852093

RESUMO

RATIONALE: Molecular mechanism underlying the autosomal recessive non-syndromic hearing loss (ARNSHL) is still plausible. Pathogenic mutations of the gap junction beta 2 protein (GJB2) are reported to be the primary causes of ARNSHL. PATIENT CONCERNS: A propositus was diagnosed as ARNSHL with bilateral congenital profound hearing loss. DIAGNOSIS: With microarray and target gene sequencing testing methods, a novel GJB2 mutant was found to be associated with ARNSHL in this Han Chinese family. INTERVENTIONS/OUTCOMES: Based on the finding in this research, prenatal screening of GJB2 mutation and genetic counseling are recommended to this family for their next pregnancy. Our interventions allow the family to plan informatively. LESSONS: In this family, we discovered 2 heterozygous carriers of c.113T>C variation in the GJB2 gene. The propositus, who had profound hearing loss, had inherited the c.113T>C variation from his normal mother and the c.235delC from his father.


Assuntos
Conexinas/genética , DNA/genética , Surdez/genética , Grupos Étnicos , Mutação , Adulto , China/epidemiologia , Conexinas/metabolismo , Análise Mutacional de DNA , Surdez/diagnóstico , Surdez/etnologia , Feminino , Humanos , Lactente , Masculino , Emissões Otoacústicas Espontâneas/fisiologia , Linhagem , Prevalência
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(11): 1094-1098, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31753091

RESUMO

This article reports the clinical features and C12orf65 gene mutations of a girl with autosomal recessive spastic paraplegia-55. The 8-year-old girl experienced disease onset at the age of 5 years and had optic atrophy as the main clinical manifestation, with slow movements in standing up and a slight duck-shaped gait. Peripheral blood DNA samples were collected from this child and her parents and brother to perform high-throughput whole-exome sequencing and high-throughput mitochondrial genome sequencing. Sanger sequencing was performed for verification. The results showed two compound heterozygous mutations, c.394C>T and c.447_449delGGAinsGT, in the C12orf65 gene. The former mutation came from her father and was a known pathogenic mutation, and the latter came from her mother and was a novel mutation which had not been reported in literature. This study expands the mutation spectrum of the C12orf65 gene and thus provides a molecular basis for the etiological diagnosis of the child and the genetic counseling of the family.


Assuntos
Proteínas Mitocondriais/genética , Fatores de Terminação de Peptídeos/genética , Paraplegia Espástica Hereditária , Criança , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação , Linhagem , Paraplegia Espástica Hereditária/genética
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1081-1084, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703130

RESUMO

OBJECTIVE: To detect pathogenic gene variants in two Chinese families with cone-rod dystrophy(CORD). METHODS: After the informed consent and comprehensive ophthalmic examinations for the patients, 3 mL peripheral blood was taken from the patients' blood vessel and DNA was extracted. The DNA was sequenced by whole-exome sequencing technology and variants were analyzed. RESULTS: Two novel compound heterozygous AIPL1 variants were detected in two patients, which were c.923T to C (p.L308P) and c.421C to T (p.Q141X) variants in Family 1, c.572T to C (p.L191P) and c.421C to T (p.Q141X) in Family 2. CONCLUSION: The results supported that AIPL1 gene variants are the main cause of the two CORD families. Whole-exome sequencing technology is a useful tool in the clinical differentiated diagnosis and genetic counseling for CORD patients.


Assuntos
Proteínas de Transporte/genética , Distrofias de Cones e Bastonetes/genética , Proteínas do Olho/genética , Proteínas Adaptadoras de Transdução de Sinal , Grupo com Ancestrais do Continente Asiático , Humanos , Mutação , Linhagem , Sequenciamento Completo do Exoma
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1085-1089, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703131

RESUMO

OBJECTIVE: To delineate the clinical and genetic features of two pedigrees affected with aromatic L-amino acid decarboxylase (AADC) deficiency. METHODS: The clinical features, family history and results of genetic testing of 2 patients with AADC deficiency were retrospectively analyzed. RESULTS: Both patients featured hypotension, developmental delay and oculogyric crisis during infancy. Genetic testing confirmed that they have respectively carried c.714+ 4 (IVS6) A to T/c.175(exon2)G TO A compound heterozygous variants and c.714+ 4(IVS6)A to T homozygous variant. CONCLUSION: The clinical manifestation of children with AADC deficiency may include hypotonia, developmental delay and paroxysmal oculogyric crisis. The combination of 3-O-methyldopa testing and variant analysis is not only very useful for early diagnosis, but also important for the evaluation of treatment effect and prognosis of the disease. Discovery of the novel variants has enriched the variant spectrum of AADC deficiency.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Descarboxilases de Aminoácido-L-Aromático/deficiência , Descarboxilases de Aminoácido-L-Aromático/genética , Testes Genéticos , Análise Mutacional de DNA , Humanos , Lactente , Linhagem , Estudos Retrospectivos
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1097-1099, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703134

RESUMO

OBJECTIVE: To explore the genetic etiology of two unrelated patients with dyschromatosis symmetrica hereditaria. METHODS: Variant analysis of the ADAR gene was carried out by Sanger sequencing. RESULTS: Patient 1 was found to harbor a c.2633_2634delCT (p.Ser878fs) in exon 8 of the ADAR gene. The same variant was not found among 100 unrelated individuals. No pathogenic variant of the ADAR gene was found in patient 2. Functional prediction of the ADAR c.2633_2634delCT (p.Ser878fs) variant indicated it to be pathogenic by losing a catalytic structural domain. CONCLUSION: The c.2633_2634delCT (p.Ser878fs) variant of the ADAR gene probably underlies the pathogenesis of DSH in one of the patients.


Assuntos
Adenosina Desaminase/genética , Transtornos da Pigmentação/congênito , Proteínas de Ligação a RNA/genética , Humanos , Mutação , Linhagem , Transtornos da Pigmentação/genética , Tomografia Computadorizada por Raios X
10.
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
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1104-1106, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703136

RESUMO

OBJECTIVE: To explore the genetic basis for a pedigree affected with X-linked adrenoleukodystrophy presenting as spastic paraplegia of the lower limbs. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and his mother. Potential variant was detected with a panel for genes associated with spastic paraplegia. Candidate variant was verified by PCR and Sanger sequencing. RESULTS: Both the proband and his mother presented with walking difficulty. A previously known variant, c.623T to A (p.V208E), was identified in the ABCD1 gene mapped on chromosome X in both. CONCLUSION: X-link adrenoleukodystrophy should be taken into account as a possible diagnosis for this pedigree.


Assuntos
Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP/genética , Adrenoleucodistrofia/genética , Feminino , Testes Genéticos , Humanos , Masculino , Linhagem , Paraplegia Espástica Hereditária
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1107-1110, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703137

RESUMO

OBJECTIVE: To explore the genetic basis for a pedigree affected with Marfan syndrome (MFS). METHODS: Clinical data of the patients was collected. With genomic DNA extracted from peripheral blood samples, potential mutation was detected by targeted exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. RESULTS: Targeted exome sequencing and Sanger sequencing revealed a missense c.649T to C(p.Trp217Arg) variant in the exon 7 of FBN1 gene, which was unreported previously. Bioinformatics analysis suggested that the variant can cause amino acid replacement and affect the structure and function of fibrillin-1. CONCLUSION: A novel missense variant of the FBN1 gene was identified, which probably underlies the autosomal dominant MFS in this pedigree.


Assuntos
Fibrilina-1/genética , Síndrome de Marfan/genética , Mutação de Sentido Incorreto , Análise Mutacional de DNA , Éxons , Fibrilinas , Humanos , Mutação , Linhagem
13.
Indian J Dent Res ; 30(4): 643-646, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31745067

RESUMO

Dentinogenesis Imperfecta and dentin dysplasia are genetic oral diseases inherited in a simple autosomal dominant mode, with high penetrance and a low mutation rate. Both of them are present with bulbous crowns, marked cervical constrictions, severe attritions, few periapical radiolucencies, and premature tooth loss. The diagnosis is based on family history, and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Here, we present a case with overlapping features of both dentinogenesis imperfecta and dentin dysplasia asserting both the anomalies to be part of the same continuum of the genetic event.


Assuntos
Displasia da Dentina , Dentinogênese Imperfeita , Dentina , Proteínas da Matriz Extracelular , Humanos , Linhagem , Fosfoproteínas , Sialoglicoproteínas
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 957-960, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598935

RESUMO

OBJECTIVE: To explore the genetic basis of a patient with early-onset Parkinson disease from a consanguineous family. METHODS: Homozygosity mapping and Sanger sequencing of cDNA were used to identify the causative mutation. RESULTS: A homozygous missense variation (c.56C>G, p.Thr19Arg) in the PARK7 gene was identified in the patient. In silico analysis suggested the c.56C>G variation to be pathogenic. CONCLUSION: Homozygous c.56C>G variation of the PARK7 gene was the disease-causing variation in this family.


Assuntos
Doença de Parkinson/genética , Proteína Desglicase DJ-1/genética , Consanguinidade , Homozigoto , Humanos , Mutação de Sentido Incorreto , Linhagem
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 961-964, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598936

RESUMO

OBJECTIVE: To analyze the clinical phenotype of a Chinese pedigree affected with Tuberous sclerosis complex (TSC) and explore pathogenic mutations of TSC1 and TSC2 gene. METHODS: Unique clinical phenotypes,the results of imaging, examination of the proband and special family history, collectively, made the constellation of features of TSC. Genomic DNA was obtained from six affected and eight unaffected members of the family and potential mutations of the TSC1 and TSC2 genes were detected by PCR-amplification of the exons and exon-intron boundaries and direct sequencing. A total of 150 normal unrelated individuals were used as controls. RESULTS: Genetic analysis documented the presence of a heterozygous mutation, c.1781_1782delTG (p.Val594GlyfsX11), in the exon 15 of TSC1 gene within all the patients of the family. This mutation was not observed in the eight unaffected family members or in the 150 unrelated control subjects from the same population , or the Human Gene Mutation Database (HGMD) and had completely co-segregated with the disease phenotype in the family. CONCLUSION: The c.1781_1782delTG mutation of TSC1 gene may be responsible for the tuberous sclerosis complex in this family. The data presented in the present study are of significance to clinicians, as well as genetic counselors, and may provide new clues for molecular diagnosis of this disease..


Assuntos
Proteína 1 do Complexo Esclerose Tuberosa/genética , Esclerose Tuberosa/genética , Análise Mutacional de DNA , Humanos , Mutação , Linhagem , Proteína 2 do Complexo Esclerose Tuberosa
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 965-969, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598937

RESUMO

OBJECTIVE: To explore the genetic basis for a family with non-syndromic autosomal recessive deafness. METHODS: The proband and her parents were subjected to physical and audiological examinations. With genomic DNA extracted from peripheral blood samples, next-generation sequencing was carried out using a panel for deafness genes. Suspected mutation was validated by Sanger sequencing and qPCR analysis of her parents. RESULTS: The proband presented bilateral severe sensorineural hearing loss at three days after birth. Her auditory threshold was 110-120 dBnHL but with absence of vestibular and retinal symptoms. Her brother also had deafness but her parents were normal. No abnormality was found upon physical examination of her family members, while audiological examination showed no middle ear or retrocochlear diseases. Next-generation sequencing identified compound heterozygous mutations of the MYO7A gene, including a previously known c.462C>A (p. Cys154Ter) and a novel EX43_46 Del, which were respectively derived from her mother and father. CONCLUSION: The compound heterozygous mutations of the MYO7A gene probably underlie the disease in this family. Our findings has enriched the mutation spectrum for non-syndromic autosomal recessive deafness 2.


Assuntos
Perda Auditiva Neurossensorial/genética , Miosinas/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação , Linhagem
17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 985-988, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598941

RESUMO

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with pachyonychia congenita (PC). METHODS: With informed consent obtained, peripheral blood samples were taken from the pedigree. Genomic DNA was extracted with a phenol/chloroform method. Based on the clinical manifestation of the patients, candidate genes for PC were selected. Potential mutation was screened by PCR and Sanger sequencing. Suspected mutation was verified in other family members by PCR-high resolution melting (HRM) analysis. Haplotype analysis using microsatellite markers was also carried out to determine the founder of the mutation. RESULTS: A heterozygous c.275A>G (Asn92Ser) mutation was discovered in exon 1 of the KRT17 gene in the proband. PCR-HRM analysis showed that all affected members were heterozygous carriers of the mutation. The same mutation was found in none of the unaffected members. Haplotype analysis and sequencing indicated the mother of the proband to be the founder. CONCLUSION: The c.275A>G (Asn92Ser) mutation of the KRT17 gene probably underlies the disease in this pedigree. Above finding has facilitated genetic counseling and prenatal diagnosis for this pedigree.


Assuntos
Queratina-17/genética , Paquioníquia Congênita/genética , Grupo com Ancestrais do Continente Asiático , Humanos , Mutação , Linhagem , Reação em Cadeia da Polimerase
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 989-992, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598942

RESUMO

OBJECTIVE: To explore the nature and origin of chromosomal copy number variants (CNVs) in a pedigree affected with mental retardation. METHODS: Genomic CNVs of the proband were analyzed by next generation sequencing (NGS). Chromosomal karyotypes of the proband and his relatives were analyzed with high-resolution karyotyping and fluorescence in situ hybridization (FISH). RESULTS: Clinical phenotypes of the proband and other patients from the pedigree included mental retardation and mild dysmorphism. The results of NGS revealed that the proband carried a 16.24 Mb microduplication at 4p16.3-15.32 and a 2.2 Mb microdeletion at 8p23.3-23.2. Other patients of the pedigree harbored the same variants, while those without the phenotypes did not harbor the variants. The results of high-resolution karyotyping and FISH revealed that the mother of the proband carried a reciprocal translocation between 4p and 8p, and her karyotype was 46,XX,t(4;8)(p16;p23). No karyotypic abnormality was detected in his father. CONCLUSION: The abnormal phenotypes of this pedigree may be attributed to 4p microduplication in conjunct with 8p microdeletion derived from a maternal balanced translocation between 4p and 8p.


Assuntos
Aberrações Cromossômicas , Duplicação Cromossômica , Testes Genéticos , Deficiência Intelectual/genética , Cromossomos Humanos Par 4 , Cromossomos Humanos Par 8 , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Linhagem , Fenótipo
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 993-995, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598943

RESUMO

OBJECTIVE: To explore the genetic etiology of a pedigree affected with tricho-rhino-phalangeal syndrome. METHODS: Next-generation sequencing (NGS) using a gene panel for hereditary osteopathies was carried out for the proband. Suspected mutation was validated in the proband and her parents by Sanger sequencing. RESULTS: A heterozygous frameshift variation c.1995dupA (p.Gly666Argfs*20) of the TRPS1 gene was detected in the proband but not in her parents. CONCLUSION: The novel c.1995dupA (p.Gly666Argfs*20) mutation of the TRPS1 gene probably underlies the disease in the proband.


Assuntos
Proteínas de Ligação a DNA/genética , Dedos/anormalidades , Mutação da Fase de Leitura , Doenças do Cabelo/genética , Síndrome de Langer-Giedion/genética , Nariz/anormalidades , Fatores de Transcrição/genética , Feminino , Humanos , Linhagem
20.
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
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