title: Novel compound heterozygous mutations in MYO7A in a Chinese family with Usher syndrome type 1.
abstract: OBJECTIVE
  To identify the disease-causing mutation(s) in a Chinese family with autosomal recessive Usher syndrome type 1 (USH1).
  
  
  METHODS
  An ophthalmic examination and an audiometric test were conducted to ascertain the phenotype of two affected siblings. The microsatellite marker D11S937, which is close to the candidate gene MYO7A (USH1B locus), was selected for genotyping. From the DNA of the proband, all coding exons and exon-intron boundaries of MYO7A were sequenced to identify the disease-causing mutation(s). Restriction fragment length polymorphism (RFLP) analysis was performed to exclude the alternative conclusion that the mutations are non-pathogenic rare polymorphisms.
  
  
  RESULTS
  Based on severe hearing impairment, unintelligible speech, and retinitis pigmentosa, a clinical diagnosis of Usher syndrome type 1 was made. The genotyping results did not exclude the USH1B locus, which suggested that the MYO7A gene was likely the gene associated with the disease-causing mutation(s) in the family. With direct DNA sequencing of MYO7A, two novel compound heterozygous mutations (c.3742G>A and c.6051+1G>A) of MYO7A were identified in the proband. DNA sequence analysis and RFLP analysis of other family members showed that the mutations cosegregated with the disease. Unaffected members, including the parents, uncle, and sister of the proband, carry only one of the two mutations. The mutations were not present in the controls (100 normal Chinese subjects=200 chromosomes) according to the RFLP analysis.
  
  
  CONCLUSIONS
  In this study, we identified two novel mutations, c.3742G>A (p.E1248K) and c.6051+1G>A (donor splice site mutation in intron 44), of MYO7A in a Chinese non-consanguineous family with USH1. The mutations cosegregated with the disease and most likely cause the phenotype in the two affected siblings who carry these mutations compound heterozygously. Our finding expands the mutational spectrum of MYO7A.
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Weirong
authors.initials: W
authors.lastname: Li
authors.forename: Fulton
authors.initials: F
authors.lastname: Wong
authors.forename: Rong
authors.initials: R
authors.lastname: Du
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.forename: Fagang
authors.initials: F
authors.lastname: Jiang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001299:Audiometry; D001483:Base Sequence; D002681:China; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005654:Fundus Oculi; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D000081412:Myosin VIIa; D009218:Myosins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D016415:Sequence Alignment; D052245:Usher Syndromes / Q000235:genetics*
chemical_list: C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009218:Myosins
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