title: Identification and functional study of a new missense mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11).
abstract: The MYO7A encodes a protein classified as an unconventional myosin. Here, we present a family with non-syndromic autosomal dominant hearing impairment that clinically resembles other previously published DFNA11 families. Affected members of the family present with an ascending audiogram affecting low and middle frequencies at young ages and then affecting all frequencies with increasing age. Genome-wide linkage analysis using Illumina Cyto-12 Chip mapped the disease locus to the DFNA11 interval in the family. A c.2003G→A (p.R668H) mutation of the MYO7A, is heterozygous in all affected family members and absent in 100 healthy individuals. Arg668His is located in a region of the myosin VIIA motor domain that is highly conserved among different species. Molecular modeling predicts that the conserved R668 residue plays important structural role in linking different lobes of motor domain together. In the actin-activated ATPase activity assay, the rate of NADH oxidation was higher in the wild-type myosin VIIA, indicating that the ATPase activity in the p.R668H mutant myosin VIIA was significantly destroyed.
authors: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
authors: Qing
authors: Q
authors: Sang
authors: Xukun
authors: X
authors: Yan
authors: Huan
authors: H
authors: Wang
authors: Ruizhi
authors: R
authors: Feng
authors: Xiang
authors: X
authors: Fei
authors: Duan
authors: D
authors: Ma
authors: Qinghe
authors: Q
authors: Xing
authors: Qiaoli
authors: Q
authors: Li
authors: Xinzhi
authors: X
authors: Zhao
authors: Li
authors: L
authors: Jin
authors: Lin
authors: L
authors: He
authors: Huawei
authors: H
authors: Li
authors: Lei
authors: L
authors: Wang
mesh_terms: D044466:Asian People / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense / Q000235:genetics*; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D010375:Pedigree; D011487:Protein Conformation
chemical_list: C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009218:Myosins
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