title: Mutation in CEP63 co-segregating with developmental dyslexia in a Swedish family.
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.affiliation: Department of Biosciences and Nutrition, and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden. elisabet.einarsdottir@ki.se.
authors.forename: Elisabet
authors.identifier: http://orcid.org/0000-0003-3101-2285
authors.initials: E
authors.lastname: Einarsdottir
authors.affiliation: Department of Psychology, Linneaus University, Växjö, Sweden.
authors.forename: Idor
authors.initials: I
authors.lastname: Svensson
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Solna, Sweden.
authors.forename: Fahimeh
authors.initials: F
authors.lastname: Darki
authors.affiliation: Department of Biosciences and Nutrition, and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Myriam
authors.initials: M
authors.lastname: Peyrard-Janvid
authors.affiliation: Department of Biosciences and Nutrition, and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden.|Bioinformatics Infrastructure for Life Sciences (BILS), Stockholm University, Stockholm, Sweden.|Science for Life Laboratory, Stockholm University, Stockholm, Sweden.|Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Lindvall
authors.affiliation: Uppsala Genome Center, Uppsala University, Uppsala, Sweden.
authors.forename: Adam
authors.initials: A
authors.lastname: Ameur
authors.affiliation: Department of Pedagogy, Linneaus University, Växjö, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Jacobsson
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Solna, Sweden.
authors.forename: Torkel
authors.initials: T
authors.lastname: Klingberg
authors.affiliation: Department of Biosciences and Nutrition, and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden.|Science for Life Laboratory, Stockholm University, Stockholm, Sweden.|Molecular Neurology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.|Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.affiliation: Department of Biosciences and Nutrition, and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Matsson
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000254:growth & development; D018797:Cell Cycle Proteins; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004410:Dyslexia / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D013548:Sweden
chemical_list: C508298:CEP63 protein, human; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins