CACNA1H Mutations in Autism Spectrum Disorders
| Autor: | Igor Splawski, David E. Clapham, Stephanie C. Stotz, Allison Cherry, Mark T. Keating, Dana S. Yoo |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
DNA Mutational Analysis
Mutation Missense Timothy syndrome Epigenetics of autism Biology behavioral disciplines and activities Biochemistry Calcium Channels T-Type mental disorders medicine CACNA1H Humans Missense mutation Heritability of autism Autistic Disorder Molecular Biology Conserved Sequence Family Health Genetics Molecular Epidemiology Calcium channel Cell Biology medicine.disease Phenotype Pedigree Electrophysiology Kinetics Case-Control Studies biology.protein Autism |
| Zdroj: | Journal of Biological Chemistry. 281:22085-22091 |
| ISSN: | 0021-9258 |
| Popis: | Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by impaired social interaction, communication skills, and restricted and repetitive behavior. The genetic causes for autism are largely unknown. Previous studies implicate CACNA1C (L-type Ca(V)1.2) calcium channel mutations in a disorder associated with autism (Timothy syndrome). Here, we identify missense mutations in the calcium channel gene CACNA1H (T-type Ca(V)3.2) in 6 of 461 individuals with ASD. These mutations are located in conserved and functionally relevant domains and are absent in 480 ethnically matched controls (p = 0.014, Fisher's exact test). Non-segregation within the pedigrees between the mutations and the ASD phenotype clearly suggest that the mutations alone are not responsible for the condition. However, functional analysis shows that all these mutations significantly reduce Ca(V)3.2 channel activity and thus could affect neuronal function and potentially brain development. We conclude that the identified mutations could contribute to the development of the ASD phenotype. |
| Databáze: | OpenAIRE |
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