Loss-of-function mutations of ILDR1 cause autosomal-recessive hearing impairment DFNB42

Guntram Borck, Atteeq Ur Rehman, Kwanghyuk Lee, Hans Martin Pogoda, Naseebullah Kakar, Simon Von Ameln, Nicolas Grillet, Michael S. Hildebrand, Zubair M. Ahmed, Gudrun Nürnberg, Muhammad Ansar, Sulman Basit, Qamar Javed, Robert J. Morell, Nabilah Nasreen, A. Eliot Shearer, Adeel Ahmad, Kimia Kahrizi, Rehan S. Shaikh, Rana A. AliShaheen N. Khan, Ingrid Goebel, Nicole C. Meyer, William J. Kimberling, Jennifer A. Webster, Dietrich A. Stephan, Martin R. Schiller, Melanie Bahlo, Hossein Najmabadi, Peter G. Gillespie, Peter Nürnberg, Bernd Wollnik, Saima Riazuddin, Richard J.H. Smith, Wasim Ahmad, Ulrich Müller, Matthias Hammerschmidt, Thomas B. Friedman, Sheikh Riazuddin, Suzanne M. Leal, Jamil Ahmad, Christian Kubisch

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)127-137
Number of pages11
JournalAmerican Journal of Human Genetics
Issue number2
StatePublished - Feb 11 2011

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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