DTNA – Meniere Disease

Meniere Disease is a chronic inner ear disorder characterized by sensorineural hearing impairment and tinnitus within episodic vertigo. Familial cases account for 5–15% of sporadic presentations and often follow an autosomal-dominant pattern. In a Spanish pedigree, whole-exome sequencing identified a heterozygous DTNA variant, c.2224G>T (p.Val742Phe), which co-segregated with disease in three affected individuals across three generations, consistent with autosomal-dominant inheritance (PMID:25305078).

In a targeted NGS panel of 68 sporadic East Asian MD patients, rare heterozygous DTNA variants were detected in a subset (4/68), absent in 100 controls, suggesting a broader but low-frequency contribution to MD susceptibility (PMID:32038468). Functional assays showed that p.Val742Phe creates a novel splice site, leading to exon 21 skipping and a truncated dystrobrevin-α isoform; patient lymphoblasts exhibited markedly reduced DTNA transcript levels and immunohistochemistry confirmed DTNA expression in rat crista ampullaris neurosensorial epithelium (PMID:25305078).

These data provide limited genetic and experimental support for DTNA as a candidate gene in autosomal-dominant familial MD. Additional multi-family studies and replication in diverse cohorts are required before DTNA can be recommended for clinical genetic testing.

References

• Human molecular genetics • 2015 • Identification of two novel mutations in FAM136A and DTNA genes in autosomal-dominant familial Meniere's disease. PMID:25305078
• Frontiers in neurology • 2019 • Rare Variants of Putative Candidate Genes Associated With Sporadic Meniere's Disease in East Asian Population. PMID:32038468

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