Whole exome sequencing identifies a novel DFNA9 mutation, C162Y

Area of Science:

• Genetics
• Otolaryngology
• Molecular Biology

Background:

• Autosomal dominant non-syndromic progressive sensorineural hearing loss, specifically DFNA9, is a significant cause of adult-onset hearing impairment.
• The genetic basis of DFNA9 is complex, with mutations in the COCH gene being a known cause.
• Understanding the specific mutations and their locations is crucial for diagnosis and potential therapeutic strategies.

Purpose of the Study:

• To identify the genetic cause of autosomal dominant non-syndromic progressive sensorineural hearing loss in a Chinese family.
• To characterize a novel mutation within the COCH gene associated with DFNA9.
• To determine if the identified mutation is novel and segregates with the disease phenotype.

Main Methods:

• Utilized next-generation high-throughput DNA sequencing (whole exome capture sequencing) combined with Sanger sequencing.
• Conducted genetic analysis on a consanguineous Chinese family presenting with hearing loss.
• Compared identified variants against public SNP databases and normal control cohorts.

Main Results:

• A novel missense mutation (c.889G>A; p.C162Y) in the seventh exon of the coagulation factor C homolog (COCH) gene was identified.
• This mutation was found to segregate with the progressive sensorineural hearing loss in the family.
• The identified mutation is located in the intervening domain of cochlin, a region previously unreported for DFNA9 mutations.

Conclusions:

• The novel COCH gene mutation is strongly implicated as the cause of autosomal dominant non-syndromic sensorineural deafness (DFNA9) in this Chinese family.
• This finding expands the mutational spectrum of DFNA9 and highlights the importance of the intervening domain of cochlin in hearing.
• Future functional studies are warranted to elucidate the precise mechanism by which this mutation leads to hearing loss.