scholarly journals A Novel Nonsense Mutation ofPOU4F3Gene Causes Autosomal Dominant Hearing Loss

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Chi Zhang ◽  
Mingming Wang ◽  
Yun Xiao ◽  
Fengguo Zhang ◽  
Yicui Zhou ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Nonsense Mutation ◽  
Autosomal Dominant ◽  
Late Onset ◽  
Stop Codon ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Chinese Family ◽  
Nonsyndromic Hearing Loss ◽  
Truncated Protein

POU4F3gene encodes a transcription factor which plays an essential role in the maturation and maintenance of hair cells in cochlea and vestibular system. Several mutations ofPOU4F3have been reported to cause autosomal dominant nonsyndromic hearing loss in recent years. In this study, we describe a pathogenic nonsense mutation located inPOU4F3in a four-generation Chinese family. Target region capture sequencing was performed to search for the candidate mutations from 81 genes related to nonsyndromic hearing loss in this family. A novel nonsense mutation ofPOU4F3, c.337C>T (p.Gln113⁎), was identified in a Chinese family characterized by late-onset progressive nonsyndromic hearing loss. The novel mutation cosegregated with hearing loss in this family and was absent in 200 ethnicity-matched controls. The mutation led to a stop codon and thus a truncated protein with no functional domains remained. Transient transfection and immunofluorescence assay revealed that the subcellular localization of the truncated protein differed markedly from normal protein, which could be the underlying reason for complete loss of its normal function. Here, we report the first nonsense mutation ofPOU4F3associated with progressive hearing loss and explored the possible underlying mechanism. Routine examination ofPOU4F3is necessary for the genetic diagnosis of hereditary hearing loss in the future.

scholarly journals A Novel Mutation in the TECTA Gene in a Chinese Family with Autosomal Dominant Nonsyndromic Hearing Loss

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e89240 ◽  
Author(s):  
Yu Su ◽  
Wen-Xue Tang ◽  
Xue Gao ◽  
Fei Yu ◽  
Zhi-Yao Dai ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Chinese Family ◽  
Nonsyndromic Hearing Loss

scholarly journals A Missense Mutation in POU4F3 Causes Midfrequency Hearing Loss in a Chinese ADNSHL Family

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Xue Gao ◽  
Jin-Cao Xu ◽  
Wei-Qian Wang ◽  
Yong-Yi Yuan ◽  
Dan Bai ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Missense Mutation ◽  
Autosomal Dominant ◽  
Genetic Diagnosis ◽  
Bioinformatic Analysis ◽  
Chinese Family ◽  
Nonsyndromic Hearing Loss ◽  
Family Routine ◽  
Targeted Capture ◽  
Normal Controls

Hereditary nonsyndromic hearing loss is extremely heterogeneous. Mutations in the POU class 4 transcription factor 3 (POU4F3) are known to cause autosomal dominant nonsyndromic hearing loss linked to the loci of DFNA15. In this study, we describe a pathogenic missense mutation in POU4F3 in a four-generation Chinese family (6126) with midfrequency, progressive, and postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining targeted capture of 129 known deafness genes, next-generation sequencing, and bioinformatic analysis, we identified POU4F3 c.602T>C (p.Leu201Pro) as the disease-causing variant. This variant cosegregated with hearing loss in other family members but was not detected in 580 normal controls or the ExAC database and could be classified as a “pathogenic variant” according to the American College of Medical Genetics and Genomics guidelines. We conclude that POU4F3 c.602T>C (p.Leu201Pro) is related to midfrequency hearing loss in this family. Routine examination of POU4F3 is necessary for the genetic diagnosis of midfrequency hearing loss.

A Novel IRF6 Frameshift Mutation in a Large Chinese Pedigree With Van der Woude syndrome

2021 ◽  
pp. 105566562110109
Author(s):  
Qi Peng ◽  
Wenyan Qin ◽  
Siping Li ◽  
Meihua Huang ◽  
Chunbao Rao ◽  
...  
Keyword(s):  
Stop Codon ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Premature Stop Codon ◽  
Chinese Family ◽  
The Novel ◽  
Protein Alignment ◽  
Van Der Woude Syndrome ◽  
Psychological Burden ◽  
Irf6 Gene

Aims: Van der Woude syndrome (VWS) is one of the most common craniofacial anomalies, causing significant functional and psychological burden to the patients. This study aimed to identify the genetic cause of VWS in a Chinese family. Methods: Whole genome sequencing (WGS) was performed to screen for pathogenic mutations. Various Bioinformatics tools were used to assess the pathogenicity of the variants. Cosegregation analysis of the candidate variant was carried out. Interpretation of variants was performed according to the American College of Medical Genetics and Genomics guidelines. Results: A novel frameshift duplication c.373_374dupAA (p.Asn125Lys fs*43) was identified in exon 4 of the interferon regulatory factor 6 (IRF6) gene in all 3 affected members, which were not found in unaffected family members. The novel mutation leads to a frameshift and a premature stop codon which caused putative truncated protein. Protein alignment indicated high evolutionary conservation of the p.N125 residue, and this mutation was predicted by online tools to be damaging and deleterious. Conclusions: This study demonstrates that the novel mutation c.373_374dupAA (p.Asn125Lysfs*43) in the IRF6 gene corresponds to the VWS in this family. The discovery of this pathogenic variant enriches the genotypic spectrum of IRF6 gene and contributes to genetic diagnosis and counseling of families with VWS.

scholarly journals Two Iranian families with a novel mutation in GJB2 causing autosomal dominant nonsyndromic hearing loss

2011 ◽  
Vol 155 (5) ◽  
pp. 1202-1211 ◽  
Author(s):  
Niloofar Bazazzadegan ◽  
Abraham M. Sheffield ◽  
Masoomeh Sobhani ◽  
Kimia Kahrizi ◽  
Nicole C. Meyer ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Nonsyndromic Hearing Loss

scholarly journals A rare novel mutation in TECTA causes autosomal dominant nonsyndromic hearing loss in a Mongolian family

2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Haihua Bai ◽  
Xukui Yang ◽  
Temuribagen ◽  
Guilan ◽  
Suyalatu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Nonsyndromic Hearing Loss

scholarly journals Identification of a novel mutation of NOG in family with proximal symphalangism and early genetic counseling

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Cong Ma ◽  
Lv Liu ◽  
Fang-Na Wang ◽  
Hai-Shen Tian ◽  
Yan Luo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Genetic Counseling ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Joint Space ◽  
Proximal Interphalangeal Joint ◽  
Chinese Family ◽  
Left Hand ◽  
Target Sequencing ◽  
The Family

Abstract Background Proximal symphalangism is a rare disease with multiple phenotypes including reduced proximal interphalangeal joint space, symphalangism of the 4th and/or 5th finger, as well as hearing loss. At present, at least two types of proximal symphalangism have been identified in the clinic. One is proximal symphalangism-1A (SYM1A), which is caused by genetic variants in Noggin (NOG), another is proximal symphalangism-1B (SYM1B), which is resulted from Growth Differentiation Factor 5 (GDF5) mutations. Case presentation Here, we reported a Chinese family with symphalangism of the 4th and/or 5th finger and moderate deafness. The proband was a 13-year-old girl with normal intelligence but symphalangism of the 4th finger in the left hand and moderate deafness. Hearing testing and inner ear CT scan suggested that the proband suffered from structural deafness. Family history investigation found that her father (II-3) and grandmother (I-2) also suffered from hearing loss and symphalangism. Target sequencing identified a novel heterozygous NOG mutation, c.690C > G/p.C230W, which was the genetic lesion of the affected family. Bioinformatics analysis and public databases filtering further confirmed the pathogenicity of the novel mutation. Furthermore, we assisted the family to deliver a baby girl who did not carry the mutation by genetic counseling and prenatal diagnosis using amniotic fluid DNA sequencing. Conclusion In this study, we identified a novel NOG mutation (c.690C > G/p.C230W) by target sequencing and helped the family to deliver a baby who did not carry the mutation. Our study expanded the spectrum of NOG mutations and contributed to genetic diagnosis and counseling of families with SYM1A.

scholarly journals A novel MYH14 mutation in a Chinese family with autosomal dominant nonsyndromic hearing loss

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Mingming Wang ◽  
Yicui Zhou ◽  
Fengguo Zhang ◽  
Zhaomin Fan ◽  
Xiaohui Bai ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Dominant ◽  
Chinese Family ◽  
Nonsyndromic Hearing Loss
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