Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate
| Autor: | D M, Warthen, E C, Moore, B M, Kamath, J J D, Morrissette, P A, Sanchez-Lara, P, Sanchez, D A, Piccoli, I D, Krantz, N B, Spinner |
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| Rok vydání: | 2006 |
| Předmět: |
JAG1
Mutation rate Genetic counseling DNA Mutational Analysis Prenatal diagnosis Biology medicine.disease_cause Cohort Studies Alagille syndrome Genetics medicine Humans Serrate-Jagged Proteins Genetic Testing In Situ Hybridization Fluorescence Genetics (clinical) Mutation Polymorphism Genetic medicine.diagnostic_test Calcium-Binding Proteins Membrane Proteins medicine.disease Alagille Syndrome Real-time polymerase chain reaction Intercellular Signaling Peptides and Proteins Jagged-1 Protein Fluorescence in situ hybridization |
| Zdroj: | Human Mutation. 27:436-443 |
| ISSN: | 1098-1004 1059-7794 |
| Popis: | Alagille syndrome (AGS) is caused by heterozygous mutations in JAG1, and mutations have been previously reported in about 70% of patients who meet clinical diagnostic criteria. We studied a cohort of 247 clinically well-defined patients, and using an aggressive and sequential screening approach we identified JAG1 mutations in 94% of individuals. Mutations were found in 232 out of 247 patients studied and 83 of the mutations were novel. This increase in the mutation rate was accomplished by combining rigorous clinical phenotyping, with a combination of mutation detection techniques, including fluorescence in situ hybridization (FISH), genomic and cDNA sequencing, and quantitative PCR. This higher rate of mutation identification has implications for clinical practice, facilitating genetic counseling, prenatal diagnosis, and evaluation of living-related liver transplant donors. Our results suggest that more aggressive screening may similarly increase the rate of mutation detection in other dominant and recessive disorders. |
| Databáze: | OpenAIRE |
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