TECTA – Autosomal dominant nonsyndromic hearing loss

Autosomal dominant nonsyndromic hearing loss (ADNSHL) is frequently caused by mutations in TECTA, encoding α-tectorin, a key component of the tectorial membrane in the inner ear. The gene–disease association has been supported by case reports, multi-family cohort screening, and functional studies demonstrating a consistent impact on tectorial membrane structure and function.

Inheritance of ADNSHL due to TECTA variants follows an autosomal dominant pattern with full penetrance. In a Mongolian family, a novel missense variant c.6016G>T (p.Asp2006Tyr) in the ZP domain co-segregated with hearing loss in all affected members and was absent in unaffected relatives and controls (PMID:25008054). A Korean pedigree identified c.710C>T (p.Thr237Ile) in the entactin domain segregating in seven affected individuals and absent in 700 matched controls (PMID:24816743).

A large multi-center study screened 372 Spanish and 835 American ADNSHL probands, identifying 23 distinct TECTA mutations across all protein domains, including recurrent alleles p.Cys1036Tyr and p.Arg1890Cys observed in multiple unrelated families with confirmed founder effects (PMID:21520338). The variant spectrum comprises primarily missense changes, with additional nonsense and frameshift mutations contributing to disease.

Functional assessment includes exon-trapping of a splice-site mutation (c.6162+3insT) demonstrating exon skipping and truncated α-tectorin in vitro (PMID:22037481). In a hepsin knockout mouse model, reduced TECTA incorporation led to tectorial membrane malformations and hearing impairment; transgenic expression of wild-type hepsin partially restored TECTA levels, membrane architecture, and auditory thresholds (PMID:39437584).

These data indicate a predominant dominant-negative mechanism for missense variants in ZP and ENT domains, disrupting protein assembly in the extracellular matrix, while splice and truncating mutations likely act via haploinsufficiency.

Overall, TECTA is Strongly implicated in ADNSHL based on ≥23 unrelated probands, multi-family segregation, diverse pathogenic variant classes, and concordant functional studies. Clinical sequencing of TECTA enables precise molecular diagnosis, family-based genetic counseling, and targeted reproductive planning.

References

• BMC medical genetics • 2014 • A rare novel mutation in TECTA causes autosomal dominant nonsyndromic hearing loss in a Mongolian family. PMID:25008054
• PloS one • 2014 • Whole-exome sequencing identifies a novel genotype-phenotype correlation in the entactin domain of the known deafness gene TECTA. PMID:24816743
• Human mutation • 2011 • DFNA8/12 caused by TECTA mutations is the most identified subtype of nonsyndromic autosomal dominant hearing loss. PMID:21520338
• Gene • 2012 • Identification and functional characterization of novel compound heterozygotic mutations in the TECTA gene. PMID:22037481
• Hearing research • 2024 • Critical role of hepsin/TMPRSS1 in hearing and tectorial membrane morphogenesis: Insights from transgenic mouse models. PMID:39437584

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