Loss-of-Function Mutations of ILDR1 Cause Autosomal-Recessive Hearing Impairment DFNB42

Borck, G; Rehman, AU; Lee, K; Pogoda, HM; Kakar, N; von Ameln, S; Grillet, N; Hildebrand, MS; Ahmed, ZM; Nurnberg, G; Ansar, M; Basit, S; Javed, Q; Morell, RJ; Nasreen, N; Shearer, AE; Ahmad, A; Kahrizi, K; Shaikh, RS; Ali, RA; Khan, SN; Goebel, I; Meyer, NC; Kimberling, WJ; Webster, JA; Stephan, DA; Schiller, MR; Bahlo, M; Najmabadi, H; Gillespie, PG; Nurnberg, P; Wollnik, B; Smith, RJH; Ahmad, W; Muller, U; Hammerschmidt, M; Friedman, TB; Riazuddin, S; Leal, SM; Ahmad, J; Kubisch, C

Author(s): Borck, G; Rehman, AU; Lee, K; Pogoda, HM; Kakar, N; von Ameln, S; Grillet, N; Hildebrand, MS; Ahmed, ZM; Nurnberg, G; Ansar, M; Basit, S; Javed, Q; Morell, RJ; Nasreen, N; Shearer, AE; Ahmad, A; Kahrizi, K; Shaikh, RS; Ali, RA; Khan, SN; Goebel, I; Meyer, NC; Kimberling, WJ; Webster, JA; Stephan, DA; Schiller, MR; Bahlo, M; Najmabadi, H; Gillespie, PG; Nurnberg, P; Wollnik, B; Smith, RJH; Ahmad, W; Muller, U; Hammerschmidt, M; Friedman, TB; Riazuddin, S; Leal, SM; Ahmad, J; Kubisch, C;
Details: Publication Year 2011-02-11,Volume 88,Issue #2,Page 127-137
Journal Title: AMERICAN JOURNAL OF HUMAN GENETICS
Publication Type: Journal Article
Abstract: By using homozygosity mapping in a consanguineous Pakistani family, we detected linkage of nonsyndromic hearing loss to a 7.6 Mb region on chromosome 3q13.31-q21.1 within the previously reported DFNB42 locus. Subsequent candidate gene sequencing identified a homozygous nonsense mutation (c.1135G>T [p.Glu379X]) in ILDR1 as the cause of hearing impairment. By analyzing additional consanguineous families with homozygosity at this locus, we detected ILDR1 mutations in the affected individuals of 10 more families from Pakistan and Iran. The identified ILDR1 variants include missense, nonsense, frameshift, and splice-site mutations as well as a start codon mutation in the family that originally defined the DFNB42 locus. ILDR1 encodes the evolutionarily conserved immunoglobulin-like domain containing receptor 1, a putative transmembrane receptor of unknown function. In situ hybridization detected expression of Ildr1, the murine ortholog, early in development in the vestibule and in hair cells and supporting cells of the cochlea. Expression in hair cell- and supporting cell-containing neurosensory organs is conserved in the zebrafish, in which the ildr1 ortholog is prominently expressed in the developing ear and neuromasts of the lateral line. These data identify loss-of-function mutations of ILDR1, a gene with a conserved expression pattern pointing to a conserved function in hearing in vertebrates, as underlying nonsyndromic prelingual sensorineural hearing impairment.
Publisher: CELL PRESS
Keywords: STIMULATED LIPOPROTEIN RECEPTOR; LINKAGE ANALYSIS; MOUSE MODELS; HAIR-CELLS; INNER-EAR; DEAFNESS; ZEBRAFISH; MICE; IDENTIFICATION; HYPERLIPIDEMIA
Publisher's Version: https://doi.org/10.1016/j.ajhg.2010.12.011
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2011-02-11 12:00:00