Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans.

Abstract

Many proteins necessary for sound transduction have been discovered through positional cloning of genes that cause deafness1–3. In this study, we report that mutations of LRTOMT are associated with profound non-syndromic hearing loss at the DFNB63 locus on human chromosome 11q13.3-q13.4. LRTOMT has two alternative reading frames and encodes two different proteins, LRTOMT1 and LRTOMT2, that are detected by Western blot analyses. LRTOMT2 is a putative methyltransferase. During evolution, novel transcripts can arise through partial or complete coalescence of genes4. We provide evidence that in the primate lineage LRTOMT evolved from the fusion of two neighboring ancestral genes, which exist as separate genes (Lrrc51and Tomt) in rodents.