@article {485,
	title = {A variant in LMX1A causes autosomal recessive severe-to-profound hearing impairment.},
	journal = {Hum Genet},
	volume = {137},
	year = {2018},
	month = {2018 Jul},
	pages = {471-478},
	abstract = {<p>Hereditary hearing impairment is a common sensory disorder that is genetically and phenotypically heterogeneous. In this study, we used a homozygosity mapping and exome sequencing strategy to study a consanguineous Pakistani family with autosomal recessive severe-to-profound hearing impairment. This led to the identification of a missense variant (p.Ile369Thr) in the LMX1A gene affecting a conserved residue in the C-terminus of the protein, which was predicted damaging by an in silico bioinformatics analysis. The p.Ile369Thr variant disrupts several C-terminal and homeodomain residue interactions, including an interaction with homeodomain residue p.Val241 that was previously found to be involved in autosomal dominant progressive HI. LIM-homeodomain factor Lmx1a is expressed in the inner ear through development, shows a progressive restriction to non-sensory epithelia, and is important in the separation of the sensory and non-sensory domains in the inner ear. Homozygous Lmx1a mutant mice (Dreher) are deaf with dysmorphic ears with an abnormal morphogenesis and fused and misshapen sensory organs; however, computed tomography performed on a hearing-impaired family member did not reveal any cochleovestibular malformations. Our results suggest that LMX1A is involved in both human autosomal recessive and dominant sensorineural hearing impairment.</p>},
	keywords = {Adolescent, Adult, Animals, Child, Disease Models, Animal, Ear, Inner, Female, Genes, Dominant, Genes, Recessive, Hearing Loss, Hearing Loss, Sensorineural, Homozygote, Humans, LIM-Homeodomain Proteins, Male, Mice, Mutation, Missense, Pedigree, Transcription Factors, Whole Exome Sequencing},
	issn = {1432-1203},
	doi = {10.1007/s00439-018-1899-7},
	author = {Schrauwen, Isabelle and Chakchouk, Imen and Liaqat, Khurram and Jan, Abid and Nasir, Abdul and Hussain, Shabir and Nickerson, Deborah A and Bamshad, Michael J and Ullah, Asmat and Ahmad, Wasim and Leal, Suzanne M}
}
