Novel CHD7 mutations contributing to the mutation spectrum in patients with CHARGE syndrome

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• 作者：Kathrin Wessels ; Bettina Bohnhorst ; Ingrid Luhmer ; Susanne Morlot ; Axel Bohring ; Jon Jonasson ; J&#xf6 ; rg T. Epplen ; Dorothea Gadzicki ; Stefanie Glaser ; Gudrun G&#xf6 ; hring ; Madeleine Mä ; lzer ; Anke
• 关键词：CHARGE syndrome ; CHD7 ; Mutation ; MLPA ; Detection rate ; Clinical variability
• 刊名：European Journal of Medical Genetics
• 出版年：2010
• 出版时间：September-October 2010
• 年：2010
• 卷：53
• 期：5
• 页码：280-285
• 全文大小：175 K

文摘

CHARGE syndrome is an autosomal dominant inherited multiple malformation disorder typically characterized by coloboma, choanal atresia, hypoplastic semicircular canal, cranial nerve defects, cardiovascular malformations and ear abnormalities. Mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene are the major cause of CHARGE syndrome. Mutation analysis was performed in 18 patients with firm or tentative clinical diagnosis of CHARGE syndrome. In this study eight mutations distributed across the gene were found. Five novel mutations – one missense (c.2936T > C), one nonsense (c.8093C > A) and three frameshift mutations (c.804_805insAT, c.1757_1770del14, c.1793delA) – were identified. As far as familial data were available these mutations were found to have arisen de novo. Comparison of the clinical features of patients with the same mutation demonstrates that expression of the phenotype is highly variable. The mutation detection rate in this study was 44.4 % in patients with a clinically established or suspected diagnosis of CHARGE syndrome.