| Summary: | Abstract We report on the genetic analysis of a Chinese family in which four male patients presented with postlingual progressive hearing loss, associated with distal muscle wasting and unsteady ataxic gait. Using whole exome sequencing, we identified a new pathogenic variant (c.1463C>T, p.Pro488Leu) in AIFM1 gene, which encodes the apoptosis-inducing factor mitochondrion-associated 1 precursor. AIFM1 gene is involved in the mitochondrial respiratory chain and cellular caspase-independent apoptosis pathway and has been reported to cause multiple phenotypes including hearing loss. The p.Pro488Leu missense variant segregated with symptoms in the pedigree, and was not found in the dbSNP database, databases of genomes and SNP in the Chinese population, in 74 patients with sporadic hearing loss, or in 108 normal individuals. We also verified that this variant AIFM1 in 293T cells enhanced cell apoptosis rates compared with 293T cells transfected with wild-type AIFM1. Different variations of AIFM1 gene give rise to different phenotypes in patients, and this is the second reported family with a variant in the C-terminal domain of AIFM1 showing the phenotype of hearing loss and peripheral neuropathy.
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