STRC – DFNB16-related Hearing Loss

STRC encodes the stereocilin protein, crucial for hair cell bundle stabilization in the inner ear. Biallelic loss-of-function variants in STRC underlie autosomal recessive nonsyndromic hearing loss 16 (STRC; autosomal recessive nonsyndromic hearing loss 16). The inheritance is autosomal recessive, consistent with homozygous deletions or compound heterozygous mutations observed in multiple families.

In a CARE case report, two siblings presented with recurrent benign paroxysmal positional vertigo and mild‐to‐moderate sensorineural hearing loss due to homozygous STRC deletions, confirmed by genomic analysis in both individuals (2 siblings) (PMID:36526540). Vestibular‐evoked myogenic potential responses were altered, supporting vestibular membrane dysfunction from stereocilin absence.

In a cohort of 94 GJB2/GJB6‐negative nonsyndromic hearing loss probands, two unrelated individuals harbored homozygous STRC deletions and one carried compound heterozygous loss-of-function alleles, totaling three independent probands with diagnostic STRC genotypes (PMID:26011646). Among sequenced variants, c.3893A>G (p.His1298Arg) was frequent in controls and is likely benign, underscoring the importance of copy number analysis for clinical interpretation.

Droplet digital PCR screening in 84 unrelated Japanese patients revealed homozygous STRC deletions in 2 individuals (2%) and heterozygous deletions in 5 (6%), yielding a combined STRC deletion prevalence of 7.7% in cases versus 0.9% in controls (PMID:31645979). These data demonstrate that STRC copy number variants are a common cause of DFNB16 in diverse populations.

Mechanistically, stereocilin is localized to vestibular kinocilia embedded in the otoconial membrane; its absence leads to membrane destabilization, as evidenced by VEMP alterations and BPPV episodes in affected patients (PMID:36526540). This pathomechanism aligns with the observed congenital mild-to-moderate sensorineural hearing loss spectrum.

No recurrent pathogenic missense variants beyond isolated reports have been confirmed. Collectively, the genetic and functional data support a strong autosomal recessive gene–disease relationship. Key Take-home: STRC loss-of-function variants are a validated cause of autosomal recessive nonsyndromic hearing loss 16 and should be included in diagnostic genetic testing panels.

References

• European annals of otorhinolaryngology, head and neck diseases • 2023 • Recurrent benign paroxysmal positional vertigo in two DFNB16 siblings: A CARE case report. PMID:36526540
• Clinical genetics • 2015 • DFNB16 is a frequent cause of congenital hearing impairment: implementation of STRC mutation analysis in routine diagnostics. PMID:26011646
• Human genome variation • 2019 • Rapid screening of copy number variations in STRC by droplet digital PCR in patients with mild-to-moderate hearing loss. PMID:31645979

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