Haploinsufficiency of the GPD2 gene in a patient with nonsyndromic mental retardation
| Autor: | Hussein Daoud, Phi Yen Vu, Patrick Vourc'h, Maïté Amy, Sylviane Védrine, Sylvain Briault, Nicolas Gruchy, Christian R. Andres, Nathalie Leporrier, Jean-Marc Constans, Nadia Bayou, Simone Saumureau, Edgar Moussaoui, Frédéric Laumonnier, Agnès Rötig |
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| Rok vydání: | 2008 |
| Předmět: |
Candidate gene
Magnetic Resonance Spectroscopy Transcription Genetic Molecular Sequence Data Chromosomal translocation Glycerolphosphate Dehydrogenase Biology Translocation Genetic Cell Line Transcription (biology) Intellectual Disability Genetics Humans Genetic Predisposition to Disease RNA Messenger Inner mitochondrial membrane Child Gene Genetics (clinical) In Situ Hybridization Fluorescence DNA Primers Base Sequence Reverse Transcriptase Polymerase Chain Reaction Breakpoint DNA Breaks Chromosome Brain Molecular biology Chromosomes Human Pair 2 Female Haploinsufficiency Chromosomes Human Pair 7 |
| Zdroj: | Human genetics. 124(6) |
| ISSN: | 1432-1203 |
| Popis: | We have investigated the chromosome abnormalities in a female patient exhibiting mild nonsyndromic mental retardation. The patient carries a de novo balanced reciprocal translocation 46,XX,t(2;7)(q24.1;q36.1). Physical mapping of the breakpoints by fluorescent in situ hybridization experiments revealed the disruption of the GPD2 gene at the 2q24.1 region. This gene encodes the mitochondrial glycerophosphate dehydrogenase (mGPDH), which is located on the outer surface of the inner mitochondrial membrane, and catalyzes the unidirectional conversion of glycerol-3-phosphate (G3P) to dihydroxyacetone phosphate with concomitant reduction of the enzyme-bound FAD. Molecular and functional studies showed approximately a twofold decrease of GPD2 transcript level as well as decreased activity of the coded mGPDH protein in lymphoblastoid cell lines of the patient compared to controls. Bioinformatics analysis allowed us to confirm the existence of a novel transcript of the GPD2 gene, designated GPD2c, which is directly disrupted by the 2q breakpoint. To validate GPD2 as a new candidate gene for mental retardation, we performed mutation screening of the GPD2 gene in 100 mentally retarded patients; however, no mutations have been identified. Nevertheless, our results propose that a functional defect of the mGPDH protein could be associated with mental retardation, suggesting that GPD2 gene could be involved in mental retardation in some cases. |
| Databáze: | OpenAIRE |
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