Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism*
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Base Sequence
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Carrier Proteins / physiology
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Chromosome Mapping
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Chromosomes, Human, Pair 5
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Cochlea / metabolism
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Contractile Proteins*
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Deafness / genetics*
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Deafness / metabolism
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Deafness / pathology
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Drosophila / genetics
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Drosophila Proteins*
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Female
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Formins
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Frameshift Mutation
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GTP-Binding Proteins / metabolism
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Gene Expression
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Hair Cells, Auditory / metabolism*
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Hair Cells, Auditory / ultrastructure
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Humans
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Male
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Microfilament Proteins / metabolism
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Molecular Sequence Data
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Pedigree
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Profilins
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RNA Splicing
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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X Chromosome
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Contractile Proteins
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DIAPH1 protein, human
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Drosophila Proteins
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Formins
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Microfilament Proteins
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PFN1 protein, human
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Profilins
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RNA, Messenger
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diaphanous protein, Drosophila
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GTP-Binding Proteins
Associated data
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GENBANK/AF051782
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GENBANK/AF052683
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GENBANK/AF052684
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GENBANK/AF052685
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GENBANK/AF052686
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GENBANK/AF052687
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GENBANK/AF053066
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GENBANK/AF053137
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GENBANK/AF053138
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GENBANK/AF053139