title: Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13.
abstract: Exome sequencing is a powerful tool for discovery of the Mendelian disease genes. Previously, we reported a novel locus for autosomal recessive non-syndromic mental retardation (NSMR) in a consanguineous family [Nolan, D.K., Chen, P., Das, S., Ober, C. and Waggoner, D. (2008) Fine mapping of a locus for nonsyndromic mental retardation on chromosome 19p13. Am. J. Med. Genet. A, 146A, 1414-1422]. Using linkage and homozygosity mapping, we previously localized the gene to chromosome 19p13. The parents of this sibship were recently included in an exome sequencing project. Using a series of filters, we narrowed the putative causal mutation to a single variant site that segregated with NSMR: the mutation was homozygous in five affected siblings but in none of eight unaffected siblings. This mutation causes a substitution of a leucine for a highly conserved proline at amino acid 182 in TECR (trans-2,3-enoyl-CoA reductase), a synaptic glycoprotein. Our results reveal the value of massively parallel sequencing for identification of novel disease genes that could not be found using traditional approaches and identifies only the seventh causal mutation for autosomal recessive NSMR.
authors.affiliation: Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA. caliskan@uchicago.edu
authors.forename: Minal
authors.initials: M
authors.lastname: Çalışkan
authors.forename: Jessica X
authors.initials: JX
authors.lastname: Chong
authors.forename: Lawrence
authors.initials: L
authors.lastname: Uricchio
authors.forename: Rebecca
authors.initials: R
authors.lastname: Anderson
authors.forename: Peixian
authors.initials: P
authors.lastname: Chen
authors.forename: Carrie
authors.initials: C
authors.lastname: Sougnez
authors.forename: Kiran
authors.initials: K
authors.lastname: Garimella
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Gabriel
authors.forename: Mark A
authors.initials: MA
authors.lastname: dePristo
authors.forename: Khalid
authors.initials: K
authors.lastname: Shakir
authors.forename: Dietrich
authors.initials: D
authors.lastname: Matern
authors.forename: Soma
authors.initials: S
authors.lastname: Das
authors.forename: Darrel
authors.initials: D
authors.lastname: Waggoner
authors.forename: Dan L
authors.initials: DL
authors.lastname: Nicolae
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
mesh_terms: D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D013570:Synaptic Membranes / Q000201:enzymology / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; D010088:Oxidoreductases