Journal
HUMAN GENETICS
Volume 137, Issue 6-7, Pages 471-478Publisher
SPRINGER
DOI: 10.1007/s00439-018-1899-7
Keywords
LMX1A; Autosomal recessive hearing impairment; Deafness; Exome sequencing
Categories
Funding
- Higher Education Commission of Pakistan
- National Institute on Deafness and Other Communication Disorders [R01 DC011651, R01 DC003594]
- National Human Genome Research Institute
- National Heart, Lung and Blood Institute [HG006493]
- National Institutes of Health [HHSN268201200008I]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available