DIAPH3 – Autosomal Dominant Auditory Neuropathy

A single 29-year-old male presented with sensorineural hearing loss, bilateral enlargement of the vestibular aqueduct and vestibular dysfunction consistent with autosomal dominant auditory neuropathy. Molecular analysis identified a novel heterozygous missense variant, c.411A>C (p.Glu137Asp), in exon 4 of DIAPH3, localizing to the Rho-GTPase-binding domain. Segregation analysis in parents and two siblings revealed the variant to be de novo (PMID:40040362).

This report represents a limited level of genetic evidence, with one proband and no proven familial segregation beyond de novo occurrence. No functional studies have yet assessed the impact of p.Glu137Asp on DIAPH3 activity or auditory pathway physiology. Further studies are needed to explore mechanism of pathogenicity and confirm the role of DIAPH3 in auditory neuropathy. Key take-home: screening of DIAPH3 should be considered in patients with unexplained autosomal dominant auditory neuropathy and EVA.

References

• Journal of audiology & otology • 2025 • Advances in Understanding the Molecular Dynamics of Autosomal Dominant Auditory Neuropathy: Unveiling a Novel DIAPH3 Gene Variant Associated With Sensorineural Hearing Loss and Bilateral Vestibular Aqueduct Enlargement. PMID:40040362

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