scholarly journals Potential digenic inheritance of familial hypertrophic cardiomyopathy identified by whole‐exome sequencing

2020 ◽  
Vol 8 (3) ◽  
Author(s):  
Ming‐Bao Ren ◽  
Xiao‐Rui Chai ◽  
Lin Li ◽  
Xin Wang ◽  
Chenghong Yin
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Digenic Inheritance ◽  
Whole Exome

scholarly journals Case Report: Whole Exome Sequencing Identifies Compound Heterozygous Variants in TSFM Gene Causing Juvenile Hypertrophic Cardiomyopathy

2022 ◽  
Vol 8 ◽  
Author(s):  
Jamie O. Yang ◽  
Hapet Shaybekyan ◽  
Yan Zhao ◽  
Xuedong Kang ◽  
Gregory A. Fishbein ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Elongation Factor ◽  
Nuclear Gene ◽  
Compound Heterozygous ◽  
Mitochondrial Translation ◽  
Translation Elongation ◽  
Whole Exome ◽  
Compound Heterozygous Variants

We report a case of hypertrophic cardiomyopathy and lactic acidosis in a 3-year-old female. Cardiac and skeletal muscles biopsies exhibited mitochondrial hyperplasia with decreased complex IV activity. Whole exome sequencing identified compound heterozygous variants, p.Arg333Trp and p.Val119Leu, in TSFM, a nuclear gene that encodes a mitochondrial translation elongation factor, resulting in impaired oxidative phosphorylation and juvenile hypertrophic cardiomyopathy.

Novel pathogenic variant of MYBPC3 responsible for hypertrophic cardiomyopathy

2021 ◽  
pp. 1-6
Author(s):  
Xiaofei Yang ◽  
Zhenghao Li ◽  
Qingfa Wang ◽  
Yongfa Zhang ◽  
Cuifen Zhao
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Data ◽  
Clinical Manifestations ◽  
Functional Change ◽  
Gene Variant ◽  
Early Screening ◽  
Strong Basis ◽  
Whole Exome

Abstract Objectives: This study aims to investigate the pathogenic gene variant in a family with hypertrophic cardiomyopathy by using whole-exome sequencing and to explore the relationship between the gene variant and clinical phenotype. Methods: Peripheral blood was collected from a family with hypertrophic cardiomyopathy, and deoxyribonucleic acid was extracted. The possible pathogenic genes were detected by whole-exome sequencing, and the variant was verified by Sanger sequencing. Functional change in the variant was predicted by bioinformatics software. Clinical data of the family members are analysed simultaneously. Results: The proband carries a novel heterozygous nonsense variant of MYBPC3:c.2731G > T (p.E911X). The analysis of amino acid conservation suggests that the variation is highly conserved. The three-dimensional protein structure shows that the variant in MYBPC3 results in the incompleteness of the fibronectintype-III2 (p872–967) domain and deletion of Ig-like C2-type 6 (p971–1065) and fibronectin type-III 3 and Ig-like C2-type 7 (p1181–1274) domains, in which p1253–1268 is predicted to have a transmembrane helix structure. Clinical data indicate that the phenotypes of variant carriers with hypertrophic cardiomyopathy are diverse, suggesting the functional damages to the protein of MYBPC3. Conclusion: The phenotypes of variant carriers with hypertrophic cardiomyopathy caused by the novel variant in MYBPC3: c.2731G > T (p.E911X) exhibit variable severity and clinical manifestations. Whole-exome sequencing can be used to comprehensive screen hypertrophic cardiomyopathy genes and provide a strong basis for early screening and accurate diagnosis and treatment of hypertrophic cardiomyopathy in children.

scholarly journals Putative Digenic GJBI2/MYO7A Inheritance of Hearing Loss Detected in a Patient with 48, XXYY Klinefelter Syndrome

2020 ◽  
Author(s):  
Tian-tian Qin ◽  
Qin Zhang ◽  
Wen-mu Hu ◽  
Muhammad Usman Janjua ◽  
Qin Long ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sex Chromosome ◽  
Chromosome Abnormality ◽  
Klinefelter Syndrome ◽  
Compound Heterozygous ◽  
Pathogenic Variants ◽  
Digenic Inheritance ◽  
Whole Exome

Abstract Background: 48, XXYY Klinefelter syndrome is a rare sex chromosome abnormality. Nonsyndromic hearing loss (NSHL) is the most frequent hereditary type of hearing impairment. There has been no report of NSHL combined with 48XXYY. The purpose of this study was to explore the underlying genetic cause in a three-generation family affected by NSHL. The proband had concomitant NSHL and 48, XXYY syndrome. The whole-exome sequencing was performed in the proband. The candidate pathogenic variants identified by whole-exome sequencing were then confirmed by Sanger sequencing and segregation analysis.Results: The proband was identified to be compound heterozygous for c.109G>A (p.V37I) variant in the GJB2 gene and additional heterozygous for the c.1039C>A (p.L347I) variants in the MYO7A gene. His mother had normal hearing and did not have any form of variant. His father and uncle, both had NSHL, were digenic compound heterozygote for the GJB2 p.V37I and MYO7A p.L347I variants, thus suggesting a possible GJB2/MYO7A digenic inheritance of NSHL in this family consist with the clinical phenotype.Conclusions: Our findings reported a putative GJB2/MYO7A digenic inheritance form of hearing loss, which expands the mutation spectrum of NSHL. This is also the first report of concomitant NSHL and 48, XXYY syndrome.

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