Usher Syndrome Type 3A

Summary

Usher syndrome type 3A is distinguished from types 1 and 2 by its progressive nature — hearing loss is not present at birth but develops and worsens over time. CLRN1 encodes clarin-1, a protein involved in synaptic function in the inner ear and retina.

Practical takeaway

Relevant if your partner is Ashkenazi Jewish or Finnish (a different CLRN1 variant, Y176X, is common in Finland). Carrier testing is available. Realised does not calculate reproductive risk or advise on reproductive decisions.

Evidence detail

What Carrier Status Means For You

You are not affected. One working copy of CLRN1 is sufficient. Standard 25/50/25 recessive inheritance applies.

Population Context

The N48K variant is an Ashkenazi Jewish founder mutation. A different variant (Y176X) makes type 3A the most common form of Usher syndrome in Finland, where it accounts for ~40% of cases. Globally, type 3A accounts for ~2-5% of all Usher syndrome except in these founder populations.

Limitations

23andMe tests 1 CLRN1 variant (N48K). The Finnish variant (Y176X) is not tested. Usher syndrome involves 9+ genes.

Sources (3)

• ClinVar: CLRN1 pathogenic/likely pathogenic variant database↗
• OMIM: #276902 (Usher Syndrome, Type IIIA)↗
• Joensuu et al. (2001), "Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3" — American Journal of Human Genetics↗