Homozygous THAP1 mutations as cause of early-onset generalized dystonia
| Autor: | Hossein Najmabadi, Katja Lohmann, Mohammad Ali Shafa, Kaveh Shafiee, Ideh Bahman, Alfredo Ramirez, Susen Winkler, Frank J. Kaiser, Christine Klein, Alev Erogullari, Alma Osmanovic, Kailish P. Bhatia, Susanne A. Schneider, Norbert Brüggemann |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Genome-wide association study Consanguinity Iran Biology medicine.disease_cause Leucine Cell Line Tumor medicine Humans Missense mutation Genetic Predisposition to Disease Histidine Gene Dystonia Genetics Mutation Reporter gene Carcinoma Homozygote Nuclear Proteins Middle Aged medicine.disease Disease gene identification Pedigree DNA-Binding Proteins Neurology Female Neurology (clinical) Apoptosis Regulatory Proteins Genome-Wide Association Study |
| Zdroj: | Movement Disorders. 26:858-861 |
| ISSN: | 0885-3185 |
| Popis: | To identify the underlying genetic cause in a consanguineous family with apparently recessively inherited dystonia, we performed genome-wide homozygosity mapping. This revealed 2 candidate regions including the THAP1 gene, where heterozygous mutations cause dystonia 6. A homozygous missense mutation in THAP1 (c.95T>A; p.Leu32His) was found in all 3 affected siblings. Symptoms started in childhood in the legs and became generalized within a few years. Three heterozygous mutation carriers were unaffected. Because THAP1 regulates the expression of the DYT1 gene, we used reporter gene assays to show that DYT1 expression was significantly increased for Leu32His. However, this increase was less pronounced than for other THAP1 mutations that cause dystonia in the heterozygous state. Our data suggest that homozygous THAP1 mutations cause dystonia and may be associated with a less severe dysfunction of the encoded protein compared with heterozygous disease-causing mutations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text