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<p>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 <i>PALM3</i> NM_001145028.2:c.314+1G&gt;A and a homozygous missense variant in <i>OTOA</i> NM_144672.4:c.1939G&gt;C p.(Gly647Arg). A minigene assay for the <i>PALM3</i> variant demonstrated aberrant splicing with exon skipping, resulting in either a frameshift or a large in-frame deletion, both consistent with loss of function and impacting all known transcripts. While the organ of Corti from 12-month-old heterozygous <i>Palm3</i> mice showed preserved overall architecture, a study describing <i>Palm3</i> knockout mice exhibit auditory dysfunction, supporting a possible auditory phenotype with loss of function. Although a dual molecular diagnosis cannot be excluded, the combined genetic, functional, and comparative data support <i>PALM3</i> as a candidate gene potentially contributing to autosomal recessive hearing loss.</p>

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PALM3 and hearing loss: a potential dual diagnosis interfering with novel gene discovery

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月29日

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  • Paria Najarzadeh Torbati,
  • Lukas Hallbrucker,
  • Michaela A. H. Hofrichter,
  • Daniel Owrang,
  • Jonas Setzke,
  • Manfred W. Kilimann,
  • Anahid Hemmatpour,
  • Mohsen Rajati,
  • Ehsan Ghayoor Karimiani,
  • Thomas Haaf,
  • Christian Vogl,
  • Barbara Vona

摘要

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 NM_144672.4:c.1939G>C p.(Gly647Arg). A minigene assay for the PALM3 variant demonstrated aberrant splicing with exon skipping, resulting in either a frameshift or a large in-frame 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, a study describing Palm3 knockout mice exhibit auditory dysfunction, supporting a possible 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 candidate gene potentially contributing to autosomal recessive hearing loss.