title: Novel CHD7 mutations contributing to the mutation spectrum in patients with CHARGE syndrome.
abstract: 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.
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Wessels
authors.forename: Bettina
authors.initials: B
authors.lastname: Bohnhorst
authors.forename: Ingrid
authors.initials: I
authors.lastname: Luhmer
authors.forename: Susanne
authors.initials: S
authors.lastname: Morlot
authors.forename: Axel
authors.initials: A
authors.lastname: Bohring
authors.forename: Jon
authors.initials: J
authors.lastname: Jonasson
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Epplen
authors.forename: Dorothea
authors.initials: D
authors.lastname: Gadzicki
authors.forename: Stefanie
authors.initials: S
authors.lastname: Glaser
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.forename: Madeleine
authors.initials: M
authors.lastname: Mälzer
authors.forename: Anke
authors.initials: A
authors.lastname: Hein
authors.forename: Mine
authors.initials: M
authors.lastname: Arslan-Kirchner
authors.forename: Manfred
authors.initials: M
authors.lastname: Stuhrmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Schmidtke
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pabst
mesh_terms: D000293:Adolescent; D058747:CHARGE Syndrome; D002648:Child; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D021141:Nucleic Acid Amplification Techniques; D010641:Phenotype; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human