Clinically isolated hearing loss as a mild phenotype of PEX26-associated peroxisomal biogenesis disorder: A case report, literature review, and in silico analysis.

BACKGROUND

Peroxisome disorders result from impaired peroxisomal function and exhibit a broad spectrum of clinical phenotypes. Recent studies suggest that mutations in PEX26, accounting for approximately 3% of cases, contribute to a clinical spectrum ranging from severe neonatal forms to clinically isolated hearing loss (CIHL), a recently recognized phenotype.

METHODS

Whole-exome sequencing and copy-number variation (CNV) analysis were performed to identify the genetic basis of bilateral SNHL without any other clinical manifestations in an Iranian man. A comprehensive literature review was also conducted to contextualize our findings.

RESULTS

We identified a homozygous PEX26 variant, c.266G > T (p.Gly89Val), in the proband, segregating with the disease in the family. In silico analyses provided computational evidence supporting a potentially deleterious effect of the variant. Sixty-one reported cases of PEX26-related disorders were identified through a literature review, with Arg98Trp being the most frequent (30%). Most variants clustered in exons 2-3 and the cytoplasmic domain.

CONCLUSION

This study identifies a novel PEX26 variant in a family with hearing loss without overt extra-auditory manifestations at the time of evaluation and provides preliminary evidence suggesting a possible association between PEX26 dysfunction and auditory phenotype.