A variant in LMX1A causes autosomal recessive severe-to-profound hearing impairment.
Hum Genet
; 137(6-7): 471-478, 2018 Jul.
Article
en En
| MEDLINE
| ID: mdl-29971487
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Proteínas con Homeodominio LIM
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Pérdida Auditiva
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Pérdida Auditiva Sensorineural
Tipo de estudio:
Etiology_studies
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Prognostic_studies
Límite:
Adolescent
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Adult
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Animals
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Hum Genet
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos