Nonsyndromic recessive deafness DFNB18 and Usher syndrome type IC are allelic mutations of USHIC.
Human chromosome 11 harbors two Usher type I loci, USHIB and USHIC, which encode myosin VIIA and harmonin, respectively. The USHIC locus overlaps the reported critical interval for nonsyndromic deafness locus DFNB18. We found an IVS12+5G-->C mutation in the USHIC gene, which is associated with nonsyndromic recessive deafness ( DFNB18) segregating in the original family, S-11/12. No other disease-associated mutation was found in the other 27 exons or in the intron-exon boundaries, and the IVS12+5G-->C mutation was not present in 200 representative unaffected individuals ascertained from the same area of India. An exon-trapping assay with a construct harboring IVS12+5G-->C generated wildtype spliced mRNA having exons 11 and 12 and mRNA that skipped exon 12. We conclude that mutations of USHIC can cause both Usher syndrome type IC and nonsyndromic recessive deafness DFNB18.
Ahmed
Zubair M
ZM
Section of Human Genetics, Laboratory of Molecular Genetics, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
Smith
Tenesha N
TN
Riazuddin
Saima
S
Makishima
Tomoko
T
Ghosh
Manju
M
Bokhari
Sirosh
S
Menon
Puthezhath S N
PS
Deshmukh
Dilip
D
Griffith
Andrew J
AJ
Riazuddin
Sheikh
S
Friedman
Thomas B
TB
Wilcox
Edward R
ER
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000483:Alleles; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003598:Cytoskeletal Proteins; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics*; D004398:Dyneins; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D009154:Mutation; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics; D013577:Syndrome; D014162:Transfection; D015837:Vestibular Diseases / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C000631455:MYO7A protein, human; D000081412:Myosin VIIa; C118970:USH1C protein, human; D004247:DNA; D009218:Myosins; D004398:Dyneins