Weston M D, Kelley P M, Overbeck L D, Wagenaar M, Orten D J, Hasson T, Chen Z Y, Corey D, Mooseker M, Sumegi J, Cremers C, Moller C, Jacobson S G, Gorin M B, Kimberling W J
Department of Genetics, Boys Town National Research Hospital, University of Nebraska Medical Center, Omaha, USA.
Am J Hum Genet. 1996 Nov;59(5):1074-83.
Usher syndrome type 1b (USH1B) is an autosomal recessive disorder characterized by congenital profound hearing loss, vestibular abnormalities, and retinitis pigmentosa. The disorder has recently been shown to be caused by mutations in the myosin VIIa gene (MYO7A) located on 11q14. In the current study, a panel of 189 genetically independent Usher I cases were screened for the presence of mutations in the N-terminal coding portion of the motor domain of MYO7A by heteroduplex analysis of 14 exons. Twenty-three mutations were found segregating with the disease in 20 families. Of the 23 mutations, 13 were unique, and 2 of the 13 unique mutations (Arg212His and Arg212Cys) accounted for the greatest percentage of observed mutant alleles (8/23, 31%). Six of the 13 mutations caused premature stop codons, 6 caused changes in the amino acid sequence of the myosin VIIa protein, and 1 resulted in a splicing defect. Three patients were homozygotes or compound heterozygotes for mutant alleles; these three cases were Tyr333Stop/Tyr333Stop, Arg212His-Arg302His/Arg212His-Arg302His, and IVS13nt-8c-->g/Glu450Gln. All the other USH1B mutations observed were simple heterozygotes, and it is presumed that the mutation on the other allele is present in the unscreened regions of the gene. None of the mutations reported here were observed in 96 unrelated control samples, although several polymorphisms were detected. These results add three patients to single case reported previously where mutations have been found in both alleles and raises the total number of unique mutations in MYO7A to 16.
1型Usher综合征（USH1B）是一种常染色体隐性疾病，其特征为先天性重度听力丧失、前庭异常和色素性视网膜炎。最近研究表明，该疾病是由位于11q14的肌球蛋白VIIa基因（MYO7A）突变引起的。在本研究中，通过对14个外显子进行异源双链分析，对189例基因独立的Usher I型病例进行筛查，以检测MYO7A运动结构域N端编码部分是否存在突变。在20个家族中发现23个突变与疾病共分离。在这23个突变中，13个是独特的，其中13个独特突变中的2个（Arg212His和Arg212Cys）占观察到的突变等位基因的最大比例（8/23，31%）。13个突变中有6个导致过早终止密码子，6个导致肌球蛋白VIIa蛋白氨基酸序列改变，1个导致剪接缺陷。3例患者为突变等位基因的纯合子或复合杂合子；这3例分别为Tyr333Stop/Tyr333Stop、Arg212His-Arg302His/Arg212His-Arg302His和IVS13nt-8c-->g/Glu450Gln。观察到的所有其他USH1B突变均为单纯杂合子，推测另一个等位基因上的突变存在于该基因未筛查的区域。在96个无关对照样本中未观察到本文报道的任何突变，尽管检测到了一些多态性。这些结果在之前报道的两个等位基因均发现突变的单病例基础上又增加了3例患者，并使MYO7A中独特突变的总数增加到16个。
