Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous.
The gene responsible for autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive hearing loss in a large Costa Rican kindred was previously localized to chromosome 5q31 and named DFNA1. Deafness in the family is associated with a protein-truncating mutation in a human homolog of the Drosophila gene diaphanous. The truncation is caused by a single nucleotide substitution in a splice donor, leading to a four-base pair insertion in messenger RNA and a frameshift. The diaphanous protein is a profilin ligand and target of Rho that regulates polymerization of actin, the major component of the cytoskeleton of hair cells of the inner ear.
Lynch
E D
ED
Department of Medicine, University of Washington, Seattle, WA 98195, USA. eric@lynch.com
Lee
M K
MK
Morrow
J E
JE
Welcsh
P L
PL
León
P E
PE
King
M C
MC
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D003051:Cochlea / Q000378:metabolism; D003285:Contractile Proteins; D003638:Deafness / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D000080865:Formins; D016368:Frameshift Mutation; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010375:Pedigree; D051304:Profilins; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014960:X Chromosome
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003285:Contractile Proteins; C108962:DIAPH1 protein, human; D029721:Drosophila Proteins; D000080865:Formins; D008840:Microfilament Proteins; C495738:PFN1 protein, human; D051304:Profilins; D012333:RNA, Messenger; C106890:diaphanous protein, Drosophila; D019204:GTP-Binding Proteins