MYO7A – Usher syndrome type 2

MYO7A is traditionally associated with Usher syndrome type 1B but emerging evidence implicates biallelic variants in MYO7A as a rare cause of Usher syndrome type 2. Inheritance is autosomal recessive, with affected individuals exhibiting congenital profound sensorineural hearing impairment and retinitis pigmentosa without vestibular involvement.

Genetic evidence stems from two unrelated families. In a three-generation Han pedigree, compound heterozygous variants c.3924+1G>C and c.6028G>A (p.Asp2010Asn) cosegregated with Usher syndrome type 2 across four affected relatives (PMID:27729122). In an independent Chinese family, a splice-site change c.1343+1G>A and a missense c.2837T>G (p.Met946Arg) were identified in trans in two affected siblings, confirming MYO7A involvement in USH2 (PMID:24831256).

While MYO7A function has been well characterized in USH1B, no dedicated functional assays for USH2-associated variants have been reported. However, both splice-site and motor-domain alterations disrupt conserved regions critical for actin binding, supporting a loss-of-function mechanism.

Taken together, two families with clear segregation of biallelic MYO7A variants provide limited but reproducible genetic support for MYO7A–Usher syndrome type 2. Although functional data specific to USH2 are lacking, the convergence of splice defects and pathogenic missense changes in key domains justify MYO7A testing in unsolved USH2 cases.

Key take-home: Biallelic MYO7A variants should be considered in diagnostic panels for Usher syndrome type 2, enabling precise genetic counseling and future therapeutic targeting.

References

• International journal of pediatric otorhinolaryngology • 2016 • Compound heterozygous MYO7A mutations segregating Usher syndrome type 2 in a Han family PMID:27729122
• PLoS one • 2014 • Novel and recurrent MYO7A mutations in Usher syndrome type 1 and type 2 PMID:24831256

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