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.

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 Association of a novel missense mutation in MYO15A with nonsyndromic hearing loss: a case report

2020 ◽  
Author(s):  
Siji Wang ◽  
Ziqi Chen ◽  
Jiaqiu Dai ◽  
Xi Ouyang ◽  
Lin Zhu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Missense Mutation ◽  
Sanger Sequencing ◽  
Three Dimensional ◽  
Sensorineural Deafness ◽  
Chinese Family ◽  
Common Disease ◽  
Compound Heterozygous ◽  
Nonsyndromic Hearing Loss ◽  
Genetic Sequencing

Abstract Background Hearing loss is a common disease globally, and more than 50% of the cases are genetic. Autosomal recessive nonsyndromic hearing loss (ARNSHL) is one of the most common types of hereditary hearing loss. Here, a novel MYO15A missense mutation was identified in a Chinese family with ARNSHL, using targeted genetic sequencing and Sanger sequencing. Case presentation: A 6-year-old girl with congenital nonsyndromic sensorineural deafness was presented from the First Affiliated hospital of Chongqing Medical University, China. We used targeted region sequencing, Sanger sequencing, functional prediction, and three-dimensional protein structure modeling to identify and verify the genes responsible for deafness in the family. Conclusions We found pathogenic compound heterozygous mutations in MYO15A, including a novel missense mutation, c.6353T > C (p.Leu2118Pro). It could provide help not only for genetic counseling but also for further understanding of the functional role of MYO15A mutations.

scholarly journals Three MYO15A Mutations Identified in One Chinese Family with Autosomal Recessive Nonsyndromic Hearing Loss

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Fengguo Zhang ◽  
Lei Xu ◽  
Yun Xiao ◽  
Jianfeng Li ◽  
Xiaohui Bai ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
High Efficiency ◽  
Cost Effective ◽  
Chinese Family ◽  
Structure Modeling ◽  
Nonsyndromic Hearing Loss ◽  
Combined Use ◽  
Targeted Capture ◽  
Capture Sequencing

Hearing impairment is one of the most common sensory disease, of which more than 50% is attributed to a genetic etiology. The goal of this research is to explore the genetic cause of a Chinese deafness pedigree who was excluded of GJB2, SLC26A4, or MtDNA12SrRNA variants. Three variants, c.3971C>A (p.A1324D), c.4011insA (p.Q1337Qfs∗22), and c.9690+1G>A, in the MYO15A gene were identified by targeted capture sequencing and Sanger sequencing, and the first two of them were novel. These variants were cosegregated with the disease in this family and absent in 200 normal hearing persons. They were concluded to be pathogenic mutations by phylogenetic analysis and structure modeling. Thus, the combined use of SNPScan assay and targeted capture sequencing is a high-efficiency and cost-effective screening procedure for hereditary hearing loss. Genetic counseling would be important for this family, and our finding would be a great supplement to the mutation spectrum of MYO15A.

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 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

scholarly journals Cochlear Implantation in a Patient with a Novel POU3F4 Mutation and Incomplete Partition Type-III Malformation

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xiuhua Chao ◽  
Yun Xiao ◽  
Fengguo Zhang ◽  
Jianfen Luo ◽  
Ruijie Wang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implantation ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Bioinformatic Analysis ◽  
Chinese Family ◽  
Whole Exome ◽  
Novel Variant ◽  
Genetic Features ◽  
The Right

Aims. This study is aimed at (1) analyzing the clinical manifestations and genetic features of a novel POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family and (2) reporting the outcomes of cochlear implantation in a patient with this mutation. Methods. A patient who was diagnosed as the IP-III malformation underwent cochlear implantation in our hospital. The genetic analysis was conducted in his family, including the whole-exome sequencing combined with Sanger sequencing and bioinformatic analysis. Clinical features, preoperative auditory and speech performances, and postoperative outcomes of cochlear implant (CI) were assessed on the proband and his family. Results. A novel variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was detected in the family, which was cosegregated with the hearing loss. This variant was absent in 200 normal-hearing persons. The phylogenetic analysis and structure modeling of Pou3f4 protein further confirmed that the novel mutation was pathogenic. The proband underwent cochlear implantation on the right ear at four years old and gained greatly auditory and speech improvement. However, the benefits of the CI declined about three and a half years postoperation. Though the right ear had been reimplanted, the outcomes were still worse than before. Conclusion. A novel frame shift variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was identified in a Chinese family with X-linked inheritance hearing loss. A patient with this mutation and IP-III malformation could get good benefits from CI. However, the outcomes of the cochlear implantation might decline as the patient grows old.

scholarly journals A Gene for Fluctuating, Progressive Autosomal Dominant Nonsyndromic Hearing Loss, DFNA16, Maps to Chromosome 2q23-24.3

1999 ◽  
Vol 65 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Kunihiro Fukushima ◽  
Norio Kasai ◽  
Yasuyoshi Ueki ◽  
Kazunori Nishizaki ◽  
Kennichi Sugata ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Dominant ◽  
Nonsyndromic Hearing Loss
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