title: Mutations in the TSGA14 gene in families with autism spectrum disorders.
abstract: Linkage to 7q has been the most robust genetic finding in familial autism. A previous scan of multiplex families with autism spectrum disorders found a linkage signal of genome-wide significance at D7S530 on 7q32. We searched a candidate imprinted region at this location for genetic variants in families with positive linkage scores. Using exon resequencing, we identified three rare potentially pathogenic variants in the TSGA14 gene, which encodes a centrosomal protein. Two variants were missense mutations (c.664C>G; p.P206A and c.766T>G; p.C240G) that changed conserved residues in the same protein domain; the third variant (c.192+5G>A) altered splicing, which resulted in a protein with an internal deletion of 16 residues and a G33D substitution. These rare TSGA14 variants are enriched in the affected subjects (6/348 patients versus 2/670 controls, Fisher's exact two tailed P = 0.022). This is the first report of a possible link of a gene with a centrosomal function with familial autism.
authors: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, 98195, USA. ok5@u.washington.edu
authors: O
authors: O
authors: Korvatska
authors: A
authors: A
authors: Estes
authors: J
authors: J
authors: Munson
authors: G
authors: G
authors: Dawson
authors: L M
authors: LM
authors: Bekris
authors: R
authors: R
authors: Kohen
authors: C-E
authors: CE
authors: Yu
authors: G D
authors: GD
authors: Schellenberg
authors: W H
authors: WH
authors: Raskind
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000208:ethnology / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: C462511:CEP41 protein, human; D011506:Proteins