PDZD7 and hearing loss: More than just a modifier.

Area of Science:

• Genetics
• Otolaryngology
• Molecular Biology

Background:

• Deafness is a prevalent sensory disorder with significant genetic heterogeneity, involving over 90 genes and 110 loci.
• Autosomal recessive non-syndromic hearing loss (ARNSHL) presents a complex genetic challenge due to its diverse etiology.

Purpose of the Study:

• To investigate the genetic causes of ARNSHL in four Iranian families.
• To identify novel genes and variants responsible for hereditary hearing loss.

Main Methods:

• Utilized linkage analysis and homozygosity mapping to pinpoint chromosomal regions.
• Employed targeted genomic enrichment and massively parallel sequencing to screen known deafness genes.
• Confirmed variant segregation through Sanger sequencing.

Main Results:

• Identified pathogenic variants in the PDZD7 gene in two families, including missense and nonsense mutations.
• Confirmed segregation of PDZD7 variants with the hearing loss phenotype in affected individuals.
• Reported a novel likely disease-causing mutation in the CIB2 gene.

Conclusions:

• Established PDZD7 mutations as a cause of ARNSHL, providing new insights into the USH2 interactome.
• Highlighted the genetic and phenotypic heterogeneity complicating the identification of deafness-causing genes.
• Emphasized the importance of comprehensive genetic screening for inherited hearing loss.