Mutation in CEP63 co-segregating with developmental dyslexia in a Swedish family.

Einarsdottir E, Svensson I, Darki F, Peyrard-Janvid M, Lindvall JM, Ameur A, Jacobsson C, Klingberg T, Kere J, Matsson H

Hum. Genet. 134 (11-12) 1239-1248 [2015-11-00; online 2015-09-25]

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.

NGI Uppsala (Uppsala Genome Center)

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PubMed 26400686

DOI 10.1007/s00439-015-1602-1

Crossref 10.1007/s00439-015-1602-1

10.1007/s00439-015-1602-1

pmc PMC4628622