scholarly journals Novel EYA4 variant in Slovak family with late onset autosomal dominant hearing loss: a case report

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Lukas Varga ◽  
Daniel Danis ◽  
Martina Skopkova ◽  
Ivica Masindova ◽  
Zuzana Slobodova ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Case Report ◽  
Autosomal Dominant ◽  
Late Onset

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 Waardenburg Syndrome: A Case Report

2019 ◽  
pp. 1-4
Author(s):  
Sara Sadiq ◽  
Azizullah Langah ◽  
Ali Akbar Siyal ◽  
Noor Ul Ain Ali
Keyword(s):  
Hearing Loss ◽  
Case Report ◽  
Sensorineural Hearing Loss ◽  
Autosomal Dominant ◽  
Congenital Deafness ◽  
Waardenburg Syndrome ◽  
Degree Relative ◽  
Heterochromia Iridis ◽  
Dystopia Canthorum ◽  
Minor Criteria

Waardenburg syndrome is an uncommon autosomal dominant or recessive disorder, distinguished by hypopigmentation of either skin or hairs or both, segmental, partial or complete heterochromia iridis or isohypochromia, hypertrichosis of eyebrow, synophrys, dystopia canthorum, broad and high nasal root and congenital deafness. The diagnostic criteria consist of major and minor criteria; major includes congenital sensorineural hearing loss, pigmentary abnormality in iris, segmental, partial or complete heterochromia iridis, isohypochromia, fore hair’s achromia, dystopia canthorum and affected first degree relative while minor criteria include congenital leukoderma, synophrys, broad and high nasal root, hypoplasia of nasal alae and premature graying of hair. Herein we report a case of two days old baby boy having uncommon pigmentation of hair and iris beside dystopia canthorum. He was diagnosed as a case of Waardenburg Syndrome type1 (WS1).

scholarly journals Clinical Characteristics and In Vitro Analysis of MYO6 Variants Causing Late-onset Progressive Hearing Loss

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 273
Author(s):  
Shin-ichiro Oka ◽  
Timothy F. Day ◽  
Shin-ya Nishio ◽  
Hideaki Moteki ◽  
Maiko Miyagawa ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Clinical Characteristics ◽  
Large Scale ◽  
Autosomal Dominant ◽  
Late Onset ◽  
Site Directed Mutagenesis ◽  
Molecular Characteristics ◽  
Progressive Hearing Loss ◽  
Cochlear Hair Cells

MYO6 is known as a genetic cause of autosomal dominant and autosomal recessive inherited hearing loss. In this study, to clarify the frequency and clinical characteristics of hearing loss caused by MYO6 gene mutations, a large-scale genetic analysis of Japanese patients with hearing loss was performed. By means of massively parallel DNA sequencing (MPS) using next-generation sequencing for 8074 Japanese families, we found 27 MYO6 variants in 33 families, 22 of which are novel. In total, 2.40% of autosomal dominant sensorineural hearing loss (ADSNHL) in families in this study (32 out of 1336) was found to be caused by MYO6 mutations. The present study clarified that most cases showed juvenile-onset progressive hearing loss and their hearing deteriorated markedly after 40 years of age. The estimated hearing deterioration was found to be 0.57 dB per year; when restricted to change after 40 years of age, the deterioration speed was accelerated to 1.07 dB per year. To obtain supportive evidence for pathogenicity, variants identified in the patients were introduced to MYO6 cDNA by site-directed mutagenesis and overexpressed in epithelial cells. They were then assessed for their effects on espin1-induced microvilli formation. Cells with wildtype myosin 6 and espin1 co-expressed created long microvilli, while co-expression with mutant constructs resulted in severely shortened microvilli. In conclusion, the present data clearly showed that MYO6 is one of the genes to keep in mind with regard to ADSNHL, and the molecular characteristics of the identified gene variants suggest that a possible pathology seems to result from malformed stereocilia of the cochlear hair cells.

Sign in / Sign up

Export Citation Format

Share Document