scholarly journals Mutations in Frizzled Class Receptor 4 Associated With Congenital Cavus Foot Deformity

2021 ◽  
Author(s):  
Wenjin Yan ◽  
Haijun Mao ◽  
Xingquan Xu ◽  
Liming Zheng ◽  
Pengjun Yu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Healthy People ◽  
The Other ◽  
Foot Deformity ◽  
Chinese Han ◽  
Whole Exome ◽  
Cavus Foot ◽  
Extrinsic Muscles

Abstract BackgroundCongenital cavus foot deformity (CFD) (congenital =present at birth) is a disease very disabling that could connected to the mobility, neurologic entities and the imbalance of synergistic intrinsic and extrinsic muscles of the patients, and the problem is even dynamic (often progressive). Here, we report the clinical and radiographic manifestations of one Chinese Han congenital CFD family and 23 congenital CFD patients. In the congenital CFD family, the proband’s mother and brother are also CFD patients. ResultsWe performed whole-exome sequencing for three patients and two healthy people in this family, and sequenced the Frizzled Class Receptor 4 (FZD4) for the other. One novel FZD4 mutation (exon2 c.1589G>A; p.G530E, NM_012193) was identified. Then mutations in FZD4 gene were further examined in 23 congenital CFD patients, and also find FZD4 mutation (FZD4:NM_012193:exon1:c.205C>T:p.H69Y) in one congenital CFD patient. ConclusionsOur study suggested that the congenital cavus foot deformity might be associated with the identified mutations in FZD4.

scholarly journals Whole exome sequencing identified mutations causing hearing loss in five consanguineous Pakistan families

2019 ◽  
Author(s):  
Yingjie Zhou ◽  
Muhammad Tariq ◽  
Sijie He ◽  
Uzma Abdullah ◽  
Jianguo Zhang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Bioinformatics Analysis ◽  
The Other ◽  
Whole Exome ◽  
Clinical Detection ◽  
Syndromic Hearing Loss ◽  
Sensory Defect

Abstract Background: Hearing loss is the most common sensory defect that affects over 6% of the population worldwide. About 50%-60% of hearing loss patients are attributed to genetic causes. Currently more than 100 genes have been reported to cause non-syndromic hearing loss. It’s possible and efficient to screen all potential disease-causing genes for hereditary hearing loss by whole exome sequencing (WES).Methods: We collected 5 consanguineous pedigrees with hearing loss from Pakistan and applied WES on selected patients for each pedigree, followed by bioinformatics analysis and Sanger validation to identify the causing genes for them.Results: Variants in 7 genes were identified and validated in these pedigrees. We identified single candidate for 3 pedigrees, which were GIPC3 (c.937T>C), LOXHD1 (c.2935G>A) and TMPRSS3 (c.941T>C). And the remaining 2 pedigrees each contained two candidates, which were TECTA (c.4045G>A) and MYO15A (c.3310G>T and c.1705G>C) for one pedigree and DFNB59 (c.494G>A) and TRIOBP (c.1952C>T) for the other pedigree. The candidates were validated in all available samples by Sanger sequencing.Conclusion: The candidate variants in hearing loss genes were validated to be co-segregated in the pedigrees, which may indicate the reasons for such patients. We also suggested that WES may be suitable strategy for hearing loss gene screening in clinical detection.

scholarly journals Whole exome sequencing identified mutations causing hearing loss in five consanguineous Pakistan families

2020 ◽  
Author(s):  
Yingjie Zhou ◽  
Muhammad Tariq ◽  
Sijie He(Former Corresponding Author) ◽  
Uzma Abdullah ◽  
Jianguo Zhang(New Corresponding Author) ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Bioinformatics Analysis ◽  
The Other ◽  
Whole Exome ◽  
Clinical Detection ◽  
Syndromic Hearing Loss ◽  
Sensory Defect

Abstract Background Hearing loss is the most common sensory defect that affects over 6% of the population worldwide. About 50%-60% of hearing loss patients are attributed to genetic causes. Currently more than 100 genes have been reported to cause non-syndromic hearing loss. It’s possible and efficient to screen all potential disease-causing genes for hereditary hearing loss by whole exome sequencing (WES). Methods We collected 5 consanguineous pedigrees with hearing loss from Pakistan and applied WES on selected patients for each pedigree, followed by bioinformatics analysis and Sanger validation to identify the causing genes for them. Results Variants in 7 genes were identified and validated in these pedigrees. We identified single candidate for 3 pedigrees, which were GIPC3 (c.937T>C), LOXHD1 (c.2935G>A) and TMPRSS3 (c.941T>C). And the remaining 2 pedigrees each contained two candidates, which were TECTA (c.4045G>A) and MYO15A (c.3310G>T and c.1705G>C) for one pedigree and DFNB59 (c.494G>A) and TRIOBP (c.1952C>T) for the other pedigree. The candidates were validated in all available samples by Sanger sequencing. Conclusion The candidate variants in hearing loss genes were validated to be co-segregated in the pedigrees, which may indicate the reasons for such patients. We also suggested that WES may be suitable strategy for hearing loss screening in clinical detection.

scholarly journals Whole-Exome Sequencing Identified a Novel Compound Heterozygous Genotype in ASL in a Chinese Han Patient with Argininosuccinate Lyase Deficiency

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Mei Zhao ◽  
Lingling Hou ◽  
Huajing Teng ◽  
Jinchen Li ◽  
Jiesi Wang ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Compound Heterozygous ◽  
Significant Activity ◽  
Argininosuccinate Lyase ◽  
Chinese Han ◽  
Lyase Deficiency ◽  
Pathogenic Variants ◽  
Whole Exome

Pathogenic variants in the argininosuccinate lyase (ASL) gene have been shown to cause argininosuccinate lyase deficiency (ASLD); therefore, sequencing analysis offers advantages for prenatal testing and counseling in families afflicted with this condition. Here, we performed a genetic analysis of an ASLD patient and his family with an aim to offer available information for clinical diagnosis. The research subjects were a 23-month-old patient with a high plasma level of citrulline and his unaffected parents. Whole-exome sequencing identified potential related ASL gene mutations in this trio. Enzymatic activity was detected spectrophotometrically by a coupled assay using arginase and measuring urea production. We identified a novel nonsynonymous mutation (c.206A>G, p.Lys69Arg) and a stop mutation (c.637C>T, p.Arg213∗) in ASL in a Chinese Han patient with ASLD. The enzymatic activity of a p.Lys69Arg ASL construct in human embryonic kidney 293T cells was significantly reduced compared to that of the wild-type construct, and no significant activity was observed for the p.Arg213∗ construct. Compound heterozygous p.Lys69Arg and p.Arg213∗ mutations that resulted in reduced ASL enzyme activity were found in a patient with ASLD. This finding expands the clinical spectrum of ASL pathogenic variants.

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