Abstract |
Developmental dyslexia is the most common learning disorder in children. Problems in reading and writing are likely due to a complex interaction of genetic and environmental factors, resulting in reduced power of studies of the genetic factors underlying developmental dyslexia. Our approach in the current study was to perform exome sequencing of affected and unaffected individuals within an extended pedigree with a familial form of developmental dyslexia. We identified a two-base mutation, causing a p.R229L amino acid substitution in the centrosomal protein 63 kDa (CEP63), co-segregating with developmental dyslexia in this pedigree. This mutation is novel, and predicted to be highly damaging for the function of the protein. 3D modelling suggested a distinct conformational change caused by the mutation. CEP63 is localised to the centrosome in eukaryotic cells and is required for maintaining normal centriole duplication and control of cell cycle progression. We found that a common polymorphism in the CEP63 gene had a significant association with brain white matter volume. The brain regions were partly overlapping with the previously reported region influenced by polymorphisms in the dyslexia susceptibility genes DYX1C1 and KIAA0319. We hypothesise that CEP63 is particularly important for brain development and might control the proliferation and migration of cells when those two events need to be highly coordinated.
|
Authors | Elisabet Einarsdottir, Idor Svensson, Fahimeh Darki, Myriam Peyrard-Janvid, Jessica M Lindvall, Adam Ameur, Christer Jacobsson, Torkel Klingberg, Juha Kere, Hans Matsson |
Journal | Human genetics
(Hum Genet)
Vol. 134
Issue 11-12
Pg. 1239-48
(Nov 2015)
ISSN: 1432-1203 [Electronic] Germany |
PMID | 26400686
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- CEP63 protein, human
- Cell Cycle Proteins
- Neoplasm Proteins
|
Topics |
- Amino Acid Sequence
- Base Sequence
- Brain
(growth & development)
- Cell Cycle Proteins
- Cell Movement
(genetics)
- Cell Proliferation
(genetics)
- Dyslexia
(genetics)
- Female
- Genetic Linkage
- Genetic Predisposition to Disease
- Humans
- Male
- Models, Molecular
- Molecular Sequence Data
- Mutation
- Neoplasm Proteins
(chemistry, genetics)
- Pedigree
- Sweden
|