PALM3 and hearing loss: a potential dual diagnosis interfering with novel gene discovery
Najarzadeh Torbati, P.; Hallbrucker, L.; Hofrichter, M. A. H.; Owrang, D.; Setzke, J.; Kilimann, M. W.; Hemmatpour, A.; Rajati, M.; Ghayoor Karimiani, E.; Haaf, T.; Vogl, C.; Vona, B.
Show abstract
Hereditary hearing loss is highly genetically heterogeneous, with emerging overlap between genes implicated in early-onset and age-related hearing loss. We report a consanguineous family with autosomal recessive, non-syndromic hearing loss in which the proband harbors a homozygous splice-site variant in PALM3 (NM_001145028.2:c.314+1G>A) and a homozygous missense variant in OTOA. A minigene assay for the PALM3 variant demonstrated aberrant splicing with exon skipping, resulting in a frameshift and a large inframe deletion, both consistent with loss of function and impacting all known transcripts. While the organ of Corti from 12-month-old heterozygous Palm3 mice showed preserved overall architecture, published Palm3 knockout mice exhibit auditory dysfunction, supporting an auditory phenotype with loss of function. Although a dual molecular diagnosis cannot be excluded, the combined genetic, functional, and comparative data support PALM3 as a strong candidate gene for autosomal recessive hearing loss.
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