scholarly journals Case report: exome sequencing achieved a definite diagnosis in a Chinese family with muscle atrophy

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hui Jiang ◽  
Chunmiao Guo ◽  
Jie Xie ◽  
Jingxin Pan ◽  
Ying Huang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Muscle Atrophy ◽  
Nonsense Mutation ◽  
Bioinformatics Analysis ◽  
Diagnostic Delay ◽  
Chinese Family ◽  
Skeletal Deformity ◽  
Her Family ◽  
Whole Exome ◽  
The Family

Abstract Background Due to large genetic and phenotypic heterogeneity, the conventional workup for Charcot-Marie-Tooth (CMT) diagnosis is often underpowered, leading to diagnostic delay or even lack of diagnosis. In the present study, we explored how bioinformatics analysis on whole-exome sequencing (WES) data can be used to diagnose patients with CMT disease efficiently. Case presentation The proband is a 29-year-old female presented with a severe amyotrophy and distal skeletal deformity that plagued her family for over 20 years since she was 5-year-old. No other aberrant symptoms were detected in her speaking, hearing, vision, and intelligence. Similar symptoms manifested in her younger brother, while her parents and her older brother showed normal. To uncover the genetic causes of this disease, we performed exome sequencing for the proband and her parents. Subsequent bioinformatics analysis on the KGGSeq platform and further Sanger sequencing identified a novel homozygous GDAP1 nonsense mutation (c.218C > G, p.Ser73*) that responsible for the family. This genetic finding then led to a quick diagnosis of CMT type 4A (CMT4A), confirmed by nerve conduction velocity and electromyography examination of the patients. Conclusions The patients with severe muscle atrophy and distal skeletal deformity were caused by a novel homozygous nonsense mutation in GDAP1 (c.218C > G, p.Ser73*), and were diagnosed as CMT4A finally. This study expanded the mutation spectrum of CMT disease and demonstrated how affordable WES could be effectively employed for the clinical diagnosis of unexplained phenotypes.

scholarly journals Identification of a Heterozygous Mutation in the TGFBI Gene in a Hui-Chinese Family with Corneal Dystrophy

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Qin Xiang ◽  
Lamei Yuan ◽  
Yanna Cao ◽  
Hongbo Xu ◽  
Yunfeiyang Li ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Transforming Growth Factor ◽  
Corneal Dystrophy ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Type I ◽  
Whole Exome ◽  
The Family

Background/Aims. Corneal dystrophies (CDs) belong to a group of hereditary heterogeneous corneal diseases which result in visual impairment due to the progressive accumulation of deposits in different corneal layers. So far, mutations in several genes have been responsible for various CDs. The purpose of this study is to identify gene mutations in a three-generation Hui-Chinese family associated with granular corneal dystrophy type I (GCD1). Methods. A three-generation Hui-Chinese pedigree with GCD1 was recruited for this study. Slit-lamp biomicroscopy, optical coherence tomography, and confocal microscopy were performed to determine the clinical features of available members. Whole exome sequencing was performed on two patients to screen for potential disease-causing variants in the family. Sanger sequencing was used to test the variant in the family members. Results. Clinical examinations demonstrated bilaterally abundant multiple grayish-white opacities in the basal epithelial and superficial stroma layers of corneas of the two patients. Whole exome sequencing revealed that a heterozygous missense mutation (c.1663C > T, p.Arg555Trp) in the transforming growth factor beta-induced gene (TGFBI) was shared by the two patients, and it cosegregated with this disease in the family confirmed by Sanger sequencing. Conclusions. The results suggested that the heterozygous TGFBI c.1663C > T (p.Arg555Trp) mutation was responsible for GCD1 in the Hui-Chinese family, which should be of great help in genetic counseling for this family.

scholarly journals A Novel Heterozygous Pathogenic Variation in CYCS Gene Cause Autosomal Dominant Non-Syndromic Thrombocytopenia 4 in a Large Chinese Family

2022 ◽  
Vol 12 ◽  
Author(s):  
Fengyu Che ◽  
Jiangang Zhao ◽  
Yujuan Zhao ◽  
Zhi Wang ◽  
Liyu Zhang ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Family Members ◽  
Clinical Signs ◽  
Missense Variant ◽  
Chinese Family ◽  
Whole Exome ◽  
The Family

Aim: To determine the etiology of a Chinese family with thrombocytopenia by analyzing the clinical features and genetic variation.Methods: Clinical profiles and genomic DNA extracts of the family members were collected for the study. Whole exome sequencing and Sanger sequencing was used to detect the associated genetic variation and verify the family co-segregation respectively. Bioinformatics analysis assessed the pathogenicity of missense mutations.Results: The study reported a 3-generation pedigree including eight family members with thrombocytopenia. The platelet counts of the patients were varied, ranging from 38 to 110 × 109/L (reference range: 150–450 x 109/L). The mean volumes and morphology of the sampled platelet were both normal. The bleeding abnormality and mitochondriopathy were not observed in all the patients. Clinical signs of thrombocytopenia were mild. A novel heterozygous missense variant c.79C > T (p.His27Tyr) was identified in CYCS gene associated with autosomal dominant thrombocytopenia.Conclusion: We report the first large family with autosomal dominant non-syndromic thrombocytopenia 4 in a Chinese family, a novel heterozygous missense variant c.79C > T (p.His27Tyr) was identified. The whole exome sequencing is an efficient tool for screening the variants specifically associated with the disease. The finding enriches the mutation spectrum of CYCS gene and laid a foundation for future studies on the correlation between genotype and phenotype.

A novel missense mutation of CRYBA1 in a northern Chinese family with inherited coronary cataract with blue punctate opacities

2021 ◽  
pp. 112067212110083
Author(s):  
Shu-Hua Ni ◽  
Juan-Mei Zhang ◽  
Jun Zhao
Keyword(s):  
Missense Mutation ◽  
High Throughput Sequencing ◽  
Bioinformatics Analysis ◽  
Genetic Defect ◽  
Kinase Domain ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Scale Invariant ◽  
The Family ◽  
Northern Chinese

Purpose: To demonstrate the underlying genetic defect that contribute to inherited cataract in a northern Chinese pedigree. Methods: The study recruited a family pedigree with a diagnosis of bilateral coronary cataract with blue punctate opacities. Fourteen family members and 100 healthy volunteers were enrolled. DNA sample of the proband in this family were analyzed by high-throughput sequencing, which was then demonstrated by Sanger sequencing in the remained people in the family and 100 controls. The functional effect of mutant genes was investigated via bioinformatics analysis, including Polymorphism Phenotyping version2 (PolyPhen-2), Protein Variation Effect Analyzer (PROVEAN v1.1.3) Scale-Invariant Feature Transform (SIFT), and Mutation Taster. Results: In this three-generation family, a novel heterozygous mutation was found in the kinase domain of CRYBA1 gene (c.340C > T, p.R114C), which was only detected in patients in the family with inherited cataract and were not detected in the remained people in the family nor in normal people. The pathogenic effect of the mutation was verified via bioinformatics analysis. Conclusion: Our study presented the molecular experiments to confirm that a novel missense mutation of c.340 C > T located in exon 4 of CRYBA1 gene results in a bilateral coronary cataract with blue punctate opacities, which enriches the mutation spectrum of CRYBA1 gene in inherited cataract and deepens the understanding of the pathogenesis of inherited cataract.

scholarly journals A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy

2021 ◽  
Author(s):  
Qing Li ◽  
Chengfeng Wang ◽  
Wei Li ◽  
Zaiqiang Zhang ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Skin Biopsy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Collagen Type Iv ◽  
Lacunar Infarcts ◽  
Whole Exome

AbstractPontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3′ untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.

Exome sequencing identifies a novel nonsense mutation of HOXD13 in a Chinese family with synpolydactyly

2017 ◽  
Vol 57 (1) ◽  
pp. 4-7 ◽  
Author(s):  
Bo Wang ◽  
Niu Li ◽  
Juan Geng ◽  
Zhigang Wang ◽  
Qihua Fu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Nonsense Mutation ◽  
Chinese Family

scholarly journals Whole-Exome Sequencing to Decipher the Genetic Heterogeneity of Hearing Loss in a Chinese Family with Deaf by Deaf Mating

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e109178 ◽  
Author(s):  
Jie Qing ◽  
Denise Yan ◽  
Yuan Zhou ◽  
Qiong Liu ◽  
Weijing Wu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Heterogeneity ◽  
Chinese Family ◽  
Whole Exome

Whole-exome sequencing identify a new mutation of MYH7 in a Chinese family with left ventricular noncompaction

Gene ◽  
2015 ◽  
Vol 558 (1) ◽  
pp. 138-142 ◽  
Author(s):  
Jing Yang ◽  
Meng Zhu ◽  
Yao Wang ◽  
Xiaofeng Hou ◽  
Hongping Wu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Left Ventricular ◽  
Chinese Family ◽  
Left Ventricular Noncompaction ◽  
New Mutation ◽  
Ventricular Noncompaction ◽  
Whole Exome

scholarly journals Striking Cardiac Phenotypic Variability in A Chinese Family With A MYH7 Splice Site Mutation

2021 ◽  
Author(s):  
Peng Tu ◽  
Hairui Sun ◽  
Xiaohang Zhang ◽  
Qian Ran ◽  
suzhen Ran ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Splice Site ◽  
Phenotypic Variability ◽  
Splice Site Mutation ◽  
Left Ventricular ◽  
Chinese Family ◽  
Site Mutation ◽  
Cardiac Phenotype ◽  
Whole Exome

Abstract Background: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare congenital heart defect (CHD), genetics defects have been found in patients with LVNC and their family members; and MYH7 is the most common genetic associated with LVNC. Methods: A trio (fetus and the parents) whole-exome sequencing (WES) was performed when the fetus was found with Ebstein's anomaly (EA), heart dilatation, perimembranous ventricular septal defects (VSD), mild seroperitoneum and single umbilical artery (SUA).Results: Whole-exome sequencing identified a maternal inherited heterozygous splice site mutation in MYH7 (NM_000257.3:c.732+1G>A). Subsequent Sanger sequencing confirmed that the mutation was heterozygous in the fetus, the old sister, the grandmother, and the mother. QPCR experiment using RNA from blood lymphocytes but were unable to amplify any product.Conclusion: This familial case underlines that the striking cardiac phenotypic of MYH7 mutation (the c.732+1G>A spice site variant) may be highly variable. The mechanistic studies which could uncover candidate genes modulating cardiac phenotype associated with LVNC/EA should be proceed.

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