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

作者：Wessels Kathrin; Bohnhorst Bettina; Luhmer Ingrid; Morlot Susanne; Bohring Axel; Jonasson Jon; Epplen Joerg T; Gadzicki Dorothea; Glaser Stefanie; Goehring Gudrun; Maelzer Madeleine; Hein Anke; Arslan Kirchner Mine; Stuhrmann Manfred; Schmidtke Joerg; Pabst Brigitte^*

来源：European Journal of Medical Genetics, 2010, 53(5): 280-285.

DOI：10.1016/j.ejmg.2010.07.002

• CHARGE syndrome
• CHD7
• Mutation
• MLPA
• Detection rate
• Clinical variability

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.

• 出版日期2010-10