A novel TECTA mutation causes ARNSHL

Area of Science:

• Genetics
• Otolaryngology
• Molecular Biology

Background:

• Autosomal recessive nonsyndromic hearing loss (ARNSHL) is a common genetic cause of sensorineural hearing loss.
• Mutations in the TECTA gene, encoding alpha-tectorin, are associated with hearing loss due to defects in the inner ear's tectorial membrane.
• DFNB21 is a specific locus for ARNSHL linked to TECTA gene mutations.

Purpose of the Study:

• To investigate the genetic cause of hearing loss in Iranian families with ARNSHL.
• To identify novel mutations in the TECTA gene associated with moderate to severe hearing loss.
• To evaluate the role of TECTA mutations in ARNSHL phenotypes.

Main Methods:

• Recruitment of 25 unrelated Iranian multiplex ARNSHL families, excluding GJB2 mutations.
• Clinical examinations including audiometric and otologic assessments to rule out syndromic hearing loss.
• Genetic linkage analysis using short tandem repeat markers for DFNB21, followed by TECTA gene sequencing in the linked family.

Main Results:

• A novel homozygous nonsense mutation (c.734G>A, p.W245×) in exon 5 of the TECTA gene was identified in one family.
• This TECTA variant co-segregated with moderate to severe hearing loss within the family.
• The identified variant was absent in 50 control individuals and met criteria for pathogenicity.

Conclusions:

• The study identified a novel TECTA mutation responsible for moderate to severe ARNSHL in an Iranian family.
• This finding expands the spectrum of TECTA-associated hearing loss phenotypes.
• Mutation screening of the TECTA gene is recommended for ARNSHL families presenting with moderate to severe hearing loss.