Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13

Minal Çalişkan, Jessica X. Chong, Lawrence Uricchio, Rebecca Anderson, Peixian Chen, Carrie Sougnez, Kiran Garimella, Stacey B. Gabriel, Mark A. DePristo, Khalid Shakir, Dietrich Matern, Soma Das, Darrel Waggoner, Dan L. Nicolae, Carole Ober

Research output: Contribution to journalArticle

75 Scopus citations

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.

Original languageEnglish (US)
Article numberddq569
Pages (from-to)1285-1289
Number of pages5
JournalHuman molecular genetics
Volume20
Issue number7
DOIs
StatePublished - Apr 1 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Çalişkan, M., Chong, J. X., Uricchio, L., Anderson, R., Chen, P., Sougnez, C., Garimella, K., Gabriel, S. B., DePristo, M. A., Shakir, K., Matern, D., Das, S., Waggoner, D., Nicolae, D. L., & Ober, C. (2011). Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13. Human molecular genetics, 20(7), 1285-1289. [ddq569]. https://doi.org/10.1093/hmg/ddq569