Insertion of beta-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness

Approximately 50% of childhood deafness is caused by mutations in specific genes. Autosomal recessive loci account for approximately 80% of nonsyndrom ic genetic deafness(1). Here Ne report the identification of a new transmem brane serine protease (TMPRSS3; also known as ECHOS1) expressed in many tis sues, including fetal cochlea, which is mutated in the families used to des cribe both the DFNB10 and DFNB8 loci. An 8-bp deletion and insertion of 18 monomeric (similar to 68-bp) beta -satellite repeat units, normally present in tandem arrays of up to several hundred kilobases on the short arms of a crocentric chromosomes, causes congenital deafness (DFNB10), A mutation in a splice-acceptor site, resulting in a 4-bp insertion in the mRNA and a fra meshift, was detected in childhood onset deafness (DFNB8). This is the firs t description of beta -satellite insertion into an active gene resulting in a pathogenic state, and the first description of a protease involved in he aring loss.