Zhou Qi, Lenger Chaeli, Smith Richard, Kimberling William J, Ye Ming, Lehmann Ordan, MacDonald Ian
Department of Ophthalmology, Peking Union Medical College, Beijing, China.
Mol Vis. 2012;18:1379-83. Epub 2012 May 31.
To identify the genetic defect in a Hutterite population from northern Alberta with Usher syndrome type I.
Complete ophthalmic examinations were conducted on two boys and two girls from two related Hutterite families diagnosed with Usher syndrome type I. DNA from patients and their parents was first evaluated for a mutation in exon 10 of the protocadherin-related 15 (PCDH15) gene (c.1471delG), previously reported in southern Alberta Hutterite patients with Usher syndrome (USH1F). Single nucleotide polymorphic linkage analysis was then used to confirm another locus, and DNA was analyzed with the Usher Chip v4.0 platform.
Severe hearing impairment, unintelligible speech, and retinitis pigmentosa with varying degrees of visual acuity and visual field loss established a clinical diagnosis of Usher syndrome type I. The patients did not carry the exon 10 mutation in the PCDH15 gene; however, with microarray analysis, a previously reported mutation (c.52C>T; p.Q18X) in the myosin VIIA (MYO7A) gene was found in the homozygous state in the affected siblings.
The finding of a MYO7A mutation in two related Hutterite families from northern Alberta provides evidence of genetic heterogeneity in Hutterites affected by Usher syndrome type I.
确定来自阿尔伯塔省北部的一个哈特人族群中患有Ⅰ型Usher综合征的遗传缺陷。
对来自两个相关哈特人家庭的两名男孩和两名女孩进行了全面眼科检查，这些孩子被诊断患有Ⅰ型Usher综合征。首先对患者及其父母的DNA进行评估，检测原钙黏蛋白相关15（PCDH15）基因第10外显子中的一个突变（c.1471delG），该突变先前在阿尔伯塔省南部患有Usher综合征（USH1F）的哈特人患者中被报道。然后使用单核苷酸多态性连锁分析来确认另一个位点，并使用Usher Chip v4.0平台对DNA进行分析。
严重听力障碍、言语不清以及伴有不同程度视力和视野丧失的视网膜色素变性确立了Ⅰ型Usher综合征的临床诊断。患者未携带PCDH15基因的第10外显子突变；然而，通过微阵列分析，在受影响的兄弟姐妹中发现了肌球蛋白VIIA（MYO7A）基因中一个先前报道的纯合状态突变（c.52C>T；p.Q18X）。
在来自阿尔伯塔省北部的两个相关哈特人家庭中发现MYO7A突变，为受Ⅰ型Usher综合征影响的哈特人存在遗传异质性提供了证据。
