Volume 78, number 2: Spectrum of CHD7 Mutations in 110 Individuals with CHARGE Syndrome and Genotype-Phenotype Correlation
6th Jan 2006, 02:53 GMT
CHARGE syndrome is a well-established multiple-malformation syndrome with distinctive consensus diagnostic criteria. Characteristic associated anomalies include ocular coloboma, choanal atresia, cranial nerve defects, distinctive external and inner ear abnormalities, hearing loss, cardiovascular malformations, urogenital anomalies, and growth retardation. Recently, mutations of the chromodomain helicase DNA-binding protein gene CHD7 were reported to be a major cause of CHARGE syndrome. We sequenced the CHD7 gene in 110 individuals who had received the clinical diagnosis of CHARGE syndrome, and we detected mutations in 64 (58%). Mutations were distributed throughout the coding exons and conserved splice sites of CHD7. Of the 64 mutations, 47 (73%) predicted premature truncation of the protein. These included nonsense and frameshift mutations, which most likely lead to haploinsufficiency. Phenotypically, the mutation-positive group was more likely to exhibit cardiovascular malformations (54 of 59 in the mutation-positive group vs. 30 of 42 in the mutation-negative group; [FORMULA]), coloboma of the eye (55 of 62 in the mutation-positive group vs. 30 of 43 in the mutation-negative group; [FORMULA]), and facial asymmetry, often caused by seventh cranial nerve abnormalities (36 of 56 in the mutation-positive group vs. 13 of 39 in the mutation-negative group; [FORMULA]). Mouse embryo whole-mount and section in situ hybridization showed the expression of Chd7 in the outflow tract of the heart, optic vesicle, facio-acoustic preganglion complex, brain, olfactory pit, and mandibular component of the first branchial arch. Microarray gene-expression analysis showed a signature pattern of gene-expression differences that distinguished the individuals with CHARGE syndrome with CHD7 mutation from the controls. We conclude that cardiovascular malformations, coloboma, and facial asymmetry are common findings in CHARGE syndrome caused by CHD7 mutation.
Volume 78, number 2: Spectrum of CHD7 Mutations in 110 Individuals with CHARGE Syndrome and Genotype-Phenotype Correlation related news:
- Volume 78, number 2: Diversity and Functional Consequences of Germline and Somatic PTPN11 Mutations in Human Disease — Am J Hum Genet Latest Issue
- Improved Power Offered by a Score Test for Linkage Disequilibrium Mapping of Quantitative-Trait Loci by Selective Genotyping — Am J Hum Genet Latest Articles
- Volume 78, number 2: SLC34A3 Mutations in Patients with Hereditary Hypophosphatemic Rickets with Hypercalciuria Predict a Key Role for the Sodium-Phosphate Cotransporter NaPi-IIc in Maintaining Phosphate Homeostasis — Am J Hum Genet Latest Issue
- More Calls For A Real Comprehensive Spectrum Policy — Techdirt
- Volume 42, number 3: Pharmacogenetics of Plasma Efavirenz Exposure after Treatment Discontinuation: An Adult AIDS Clinical Trials Group Study — Clin Infect Dis Latest Issue
- Volume 78, number 2: Hereditary Hypophosphatemic Rickets with Hypercalciuria Is Caused by Mutations in the Sodium-Phosphate Cotransporter Gene SLC34A3 — Am J Hum Genet Latest Issue
- Volume 78, number 2: Mutations in the Translated Region of the Lactase Gene (LCT) Underlie Congenital Lactase Deficiency — Am J Hum Genet Latest Issue
- Volume 78, number 2: Erratum to "Search for Haplotype Interactions That Influence Susceptibility to Type 1 Diabetes, through use of Unphased Genotype Data" by Zhang et al. (73: 1385-1401). — Am J Hum Genet Latest Issue
- Down syndrome more common, says CDC — KeralaNext: Health
- CDC: Down Syndrome More Common Than Once Thought — WXII12.com - Health