Mutations of ESPN cause autosomal recessive deafness and vestibular dysfunction.
We mapped a human deafness locus DFNB36 to chromosome 1p36.3 in two consanguineous families segregating recessively inherited deafness and vestibular areflexia. This phenotype co-segregates with either of two frameshift mutations, 1988delAGAG and 2469delGTCA, in ESPN, which encodes a calcium-insensitive actin-bundling protein called espin. A recessive mutation of ESPN is known to cause hearing loss and vestibular dysfunction in the jerker mouse. Our results establish espin as an essential protein for hearing and vestibular function in humans. The abnormal vestibular phenotype associated with ESPN mutations will be a useful clinical marker for refining the differential diagnosis of non-syndromic deafness.
Section on Human Genetics, LMG, NIDCD, NIH, Rockville, MD 20850, USA.
S
S
Naz
A J
AJ
Griffith
S
S
Riazuddin
L L
LL
Hampton
J F
JF
Battey
S N
SN
Khan
S
S
Riazuddin
E R
ER
Wilcox
T B
TB
Friedman
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D005808:Genes, Recessive / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D010375:Pedigree; D051381:Rats; D016415:Sequence Alignment; D015837:Vestibular Diseases / Q000235:genetics*
C493274:ESPN protein, human; C472022:Espn protein, rat; D008840:Microfilament Proteins; C104108:espin protein, mouse