Novel compound heterozygous mutations in MYO7A in a Chinese family with Usher syndrome type 1
Novel compound heterozygous mutations in MYO7A in a Chinese family with Usher syndrome type 1
复制标题
中国 1 型 Usher 综合征家系 MYO7A 新型复合杂合突变
作者：
Liu, Mugen;Li, Pengcheng;Liu, Ying;Li, Weirong;Wong, Fulton;Du, Rong;Wang, Lei;Li, Chang;Jiang, Fagang
目的对1个常染色体隐性遗传Usher综合征1型（USH 1）家系进行致病基因突变的鉴定。方法对两名患病同胞进行眼科检查和听力测试，以确定其表型。选择与候选基因MYO 7A（USH 1B位点）相近的微卫星标记D11 S937进行基因分型。从先证者的DNA中，对MYO 7A的所有编码外显子和外显子-内含子边界进行测序，以确定致病突变。进行限制性片段长度多态性（RFLP）分析，以排除突变为非致病性罕见多态性的替代结论。结果根据严重听力障碍、言语障碍和视网膜色素变性，临床诊断为Usher综合征1型。基因分型结果没有排除USH 1B位点，这表明MYO 7A基因可能是与该家族中致病突变相关的基因。通过对MYO 7A基因直接测序，在先证者中发现了两个新的MYO 7A复合杂合突变（c.3742G>A和c.6051+1G>A）。DNA序列分析和其他家族成员的RFLP分析表明，突变与疾病共分离。未受影响的成员，包括先证者的父母、叔叔和姐姐，只携带两种突变中的一种。根据RFLP分析，在对照组（100名正常中国人=200条染色体）中不存在突变。结论在一个中国人USH 1非血缘家系中发现MYO 7A基因的两个新突变，即c.3742G>A（p.E1248K）和c.6051+1G>A（内含子44的供体剪接位点突变）。这些突变与疾病共分离，并且很可能导致携带这些突变的两个受影响的兄弟姐妹异源复合的表型。我们的发现扩展了MYO 7A的突变谱。
Purpose 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.
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影响因子：
4
作者：
Le Quesne Stabej P;Saihan Z;Rangesh N;Steele-Stallard HB;Ambrose J;Coffey A;Emmerson J;Haralambous E;Hughes Y;Steel KP;Luxon LM;Webster AR;Bitner-Glindzicz M
通讯作者：
Bitner-Glindzicz M
影响因子：
9.8
作者：
Ahmed, ZM;Riazuddin, S;Wilcox, ER
通讯作者：
Wilcox, ER
影响因子：
--
作者：
Lily E Soni;C. Warren;C. Bucci;D. Orten;T. Hasson
通讯作者：
Lily E Soni;C. Warren;C. Bucci;D. Orten;T. Hasson
影响因子：
30.8
作者：
Verpy, E;Leibovici, M;Petit, C
通讯作者：
Petit, C
影响因子：
4
作者：
Jaijo, T.;Aller, E.;Millan, J. M.
通讯作者：
Millan, J. M.