Back to Search
Start Over
A focal epilepsy and intellectual disability syndrome is due to a mutation in TBC1D24.
- Source :
-
American journal of human genetics [Am J Hum Genet] 2010 Sep 10; Vol. 87 (3), pp. 371-5. - Publication Year :
- 2010
-
Abstract
- We characterized an autosomal-recessive syndrome of focal epilepsy, dysarthria, and mild to moderate intellectual disability in a consanguineous Arab-Israeli family associated with subtle cortical thickening. We used multipoint linkage analysis to map the causative mutation to a 3.2 Mb interval within 16p13.3 with a LOD score of 3.86. The linked interval contained 160 genes, many of which were considered to be plausible candidates to harbor the disease-causing mutation. To interrogate the interval in an efficient and unbiased manner, we used targeted sequence enrichment and massively parallel sequencing. By prioritizing unique variants that affected protein translation, a pathogenic mutation was identified in TBC1D24 (p.F251L), a gene of unknown function. It is a member of a large gene family encoding TBC domain proteins with predicted function as Rab GTPase activators. We show that TBC1D24 is expressed early in mouse brain and that TBC1D24 protein is a potent modulator of primary axonal arborization and specification in neuronal cells, consistent with the phenotypic abnormality described.<br /> (2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Animals
Axons metabolism
Carrier Proteins chemistry
Cell Shape
Chromosome Mapping
Female
GTPase-Activating Proteins chemistry
Humans
Infant
Male
Membrane Proteins
Mice
Molecular Sequence Data
Nerve Tissue Proteins
Neurons pathology
Open Reading Frames genetics
Pedigree
Syndrome
Carrier Proteins genetics
Epilepsies, Partial complications
Epilepsies, Partial genetics
GTPase-Activating Proteins genetics
Intellectual Disability complications
Intellectual Disability genetics
Mutation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6605
- Volume :
- 87
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 20797691
- Full Text :
- https://doi.org/10.1016/j.ajhg.2010.08.001