Loss-of-function mutations of ILDR1 cause autosomal-recessive hearing impairment DFNB42.
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Loss-of-function mutations of ILDR1 cause autosomal-recessive hearing impairment DFNB42. / Borck, Guntram; Atteeq, Ur Rehman; Lee, Kwanghyuk; Pogoda, Hans-Martin; Kakar, Naseebullah; von Ameln, Simon; Grillet, Nicolas; Hildebrand, Michael S; Ahmed, Zubair M; Nürnberg, Gudrun; Ansar, Muhammad; Basit, Sulman; Javed, Qamar; Morell, Robert J; Nasreen, Nabilah; Shearer, A Eliot; Ahmad, Adeel; Kahrizi, Kimia; Shaikh, Rehan S; Ali, Rana A; Khan, Shaheen N; Goebel, Ingrid; Meyer, Nicole C; Kimberling, William J; Webster, Jennifer A; Stephan, Dietrich A; Schiller, Martin R; Bahlo, Melanie; Najmabadi, Hossein; Gillespie, Peter G; Nürnberg, Peter; Wollnik, Bernd; Riazuddin, Saima; Smith, Richard J H; Ahmad, Wasim; Müller, Ulrich; Hammerschmidt, Matthias; Friedman, Thomas B; Riazuddin, Sheikh; Leal, Suzanne M; Ahmad, Jamil; Kubisch, Christian.
In: AM J HUM GENET, Vol. 88, No. 2, 2, 2011, p. 127-137.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Loss-of-function mutations of ILDR1 cause autosomal-recessive hearing impairment DFNB42.
AU - Borck, Guntram
AU - Atteeq, Ur Rehman
AU - Lee, Kwanghyuk
AU - Pogoda, Hans-Martin
AU - Kakar, Naseebullah
AU - von Ameln, Simon
AU - Grillet, Nicolas
AU - Hildebrand, Michael S
AU - Ahmed, Zubair M
AU - Nürnberg, Gudrun
AU - Ansar, Muhammad
AU - Basit, Sulman
AU - Javed, Qamar
AU - Morell, Robert J
AU - Nasreen, Nabilah
AU - Shearer, A Eliot
AU - Ahmad, Adeel
AU - Kahrizi, Kimia
AU - Shaikh, Rehan S
AU - Ali, Rana A
AU - Khan, Shaheen N
AU - Goebel, Ingrid
AU - Meyer, Nicole C
AU - Kimberling, William J
AU - Webster, Jennifer A
AU - Stephan, Dietrich A
AU - Schiller, Martin R
AU - Bahlo, Melanie
AU - Najmabadi, Hossein
AU - Gillespie, Peter G
AU - Nürnberg, Peter
AU - Wollnik, Bernd
AU - Riazuddin, Saima
AU - Smith, Richard J H
AU - Ahmad, Wasim
AU - Müller, Ulrich
AU - Hammerschmidt, Matthias
AU - Friedman, Thomas B
AU - Riazuddin, Sheikh
AU - Leal, Suzanne M
AU - Ahmad, Jamil
AU - Kubisch, Christian
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Genotype
KW - Mice
KW - Pedigree
KW - Consanguinity
KW - Lod Score
KW - Chromosome Mapping
KW - In Situ Hybridization
KW - Genetic Linkage
KW - Zebrafish
KW - Genes, Recessive/genetics
KW - Genetic Predisposition to Disease
KW - Hearing Loss/genetics
KW - Receptors, Cell Surface/genetics
KW - Chromosomes, Human, Pair 3/genetics
KW - Codon, Nonsense/genetics
KW - Ear, Inner
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Genotype
KW - Mice
KW - Pedigree
KW - Consanguinity
KW - Lod Score
KW - Chromosome Mapping
KW - In Situ Hybridization
KW - Genetic Linkage
KW - Zebrafish
KW - Genes, Recessive/genetics
KW - Genetic Predisposition to Disease
KW - Hearing Loss/genetics
KW - Receptors, Cell Surface/genetics
KW - Chromosomes, Human, Pair 3/genetics
KW - Codon, Nonsense/genetics
KW - Ear, Inner
M3 - SCORING: Journal article
VL - 88
SP - 127
EP - 137
JO - AM J HUM GENET
JF - AM J HUM GENET
SN - 0002-9297
IS - 2
M1 - 2
ER -
