Novel CHD7 mutations contributing to the mutation spectrum in patients with CHARGE syndrome.
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.
Wessels
Kathrin
K
Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
Bohnhorst
Bettina
B
Luhmer
Ingrid
I
Morlot
Susanne
S
Bohring
Axel
A
Jonasson
Jon
J
Epplen
Jörg T
JT
Gadzicki
Dorothea
D
Glaser
Stefanie
S
Göhring
Gudrun
G
Mälzer
Madeleine
M
Hein
Anke
A
Arslan-Kirchner
Mine
M
Stuhrmann
Manfred
M
Schmidtke
Jörg
J
Pabst
Brigitte
B
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
D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human