Novel PEX26 Variant Linked to Isolated Hearing Loss in Iranian Man

A single genetic change in the PEX26 gene has been identified as the likely cause of bilateral sensorineural hearing loss in an Iranian man who showed no other clinical manifestations at the time of evaluation. The finding, reported in Molecular Biology Reports, suggests that PEX26-associated peroxisomal biogenesis disorder can present as clinically isolated hearing loss (CIHL), a recently recognized and unusually mild phenotype within a group of conditions otherwise known for severe, multi-system disease.

Peroxisome disorders arise when peroxisomes, cellular compartments that carry out essential metabolic functions, fail to form or operate properly. The resulting conditions span a broad clinical spectrum, from severe neonatal presentations to milder forms. Mutations in PEX26, which encodes a protein involved in peroxisome assembly, account for approximately 3% of such cases. The new study used whole-exome sequencing together with copy-number variation analysis to search for the genetic basis of the patient’s hearing loss, and the researchers supplemented their laboratory work with a review of previously published cases.

Sequencing revealed a homozygous PEX26 variant, c.266G > T, which changes the amino acid glycine at position 89 to valine (p.Gly89Val). The variant segregated with the disease in the family, meaning family members carrying the change showed the associated hearing phenotype. Because the substitution had not been described before, the team turned to computational (in silico) analyses, which provided evidence supporting a potentially deleterious effect of the variant on the protein. The authors stress that this constitutes preliminary evidence suggesting a possible association between PEX26 dysfunction and the auditory phenotype, rather than a definitive causal proof.

The literature review identified 61 previously reported cases of PEX26-related disorders. Among the variants documented in those cases, Arg98Trp was the most frequent, appearing in 30% of reports. The authors also observed that most variants clustered in exons 2 and 3 of the gene and in the region encoding the cytoplasmic domain of the protein, a pattern that may help guide future interpretation of newly discovered PEX26 changes.

The case is notable because the patient presented with hearing impairment alone, without overt extra-auditory manifestations when he was assessed. That presentation places him at the mildest end of the PEX26 disease spectrum described so far. The authors conclude that their study identifies a novel PEX26 variant in a family with isolated hearing loss and adds to the growing recognition that peroxisomal biogenesis disorders can surface in the clinic as apparently isolated sensorineural hearing loss.

Subject of Research: A novel PEX26 gene variant associated with isolated hearing loss as a mild form of peroxisomal biogenesis disorder

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

Article References: Zahedi Abghari, F., Esmaeilzadeh, E., Mohseni, M., Robat-Jazi, B., Biglari, S., Astaraki, F., Khorram Khorshid, H. R., & Najafipour, R. (2026). Clinically isolated hearing loss as a mild phenotype of PEX26-associated peroxisomal biogenesis disorder: A case report, literature review, and in silico analysis. Molecular Biology Reports, 53(1), Article 1774. https://doi.org/10.1007/s11033-026-12878-5

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12878-5

Keywords: PEX26, peroxisomal biogenesis disorder, hearing loss, whole-exome sequencing, genetics, in silico analysis, case report, sensorineural hearing loss, literature review, rare disease, Clinically, isolated