Autosomal Recessive Nonsyndromic Hearing Impairment due to a Novel Deletion in theRDXGene

摘要

TheRDXgene anchors cytoskeletal actin of stereocilia to hair cell transmembrane and is responsible for autosomal recessive nonsyndromic hearing impairment (ARNSHI) due to DFNB24. A genome scan was performed using DNA samples from a consanguineous Pakistani family with ARNSHI. A significant maximum two-point LOD score of 4.5(θ=0)and multipoint LOD score of 5.8 were achieved at marker D11S1998 (chr11 : 117.20 Mb). The region of homozygosity is bounded by markers D11S2000 (105.06 Mb) and D11S4464 (123.13 Mb) and contains the NSHI genesTECTAandRDX. Although no potentially causal variants were identified in theTECTAgene, within theRDXgene a novel deletion c.1076_1079delTTAA (p.Ile359Lysfs*6) was identified. TheRDXdeletion segregates with ARNSHI within the family and was not observed in 500 control chromosomes. It is predicted to cause premature truncation of radixin at theα-helical domain and to result in nonfunctional transcripts within the cochlea.RDXisoforms which encode the coiled-coil region of theα-helical domain are deemed necessary for proper function of hair cell stereocilia.