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          Institute: MPI für molekulare Genetik     Collection: Department of Human Molecular Genetics     Display Documents



  history
ID: 408332.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
A defect in the TUSC3 gene is associated with autosomal recessive mental retardation
Authors:Garshasbi, Masoud; Hadavi, Valeh; Habibi, Haleh; Kahrizi, Kimia; Kariminejad, Roxana; Behjati, Farkhondeh; Tzschach, Andreas; Najmabadi, Hossein; Ropers, Hans-Hilger; Kuss, Andreas Walter
Language:English
Research Context:Report
Date of Publication (YYYY-MM-DD):2008-05-01
Title of Journal:The American Journal of Human Genetics
Journal Abbrev.:Am J Hum Genet
Volume:82
Issue / Number:5
Start Page:1158
End Page:1164
Copyright:2008 The American Society of Human Genetics. All rights reserved.
Review Status:not specified
Audience:Experts Only
Abstract / Description:Recent studies have shown that autosomal recessive mental retardation (ARMR) is extremely heterogeneous, and there is reason to believe that the number of underlying gene defects goes into the thousands. To date, however, only four genes have been implicated in nonsyndromic ARMR (NS-ARMR): PRSS12 (neurotrypsin), CRBN (cereblon), CC2D1A, and GRIK2. As part of an ongoing systematic study aiming to identify ARMR genes, we investigated a large consanguineous family comprising seven patients with nonsyndromic ARMR in four sibships. Genome-wide SNP typing enabled us to map the relevant genetic defect to a 4.6 Mbp interval on chromosome 8. Haplotype analyses and copy-number studies led to the identification of a homozygous deletion partly removing TUSC3 (N33) in all patients. All obligate carriers of this family were heterozygous, but none of 192 unrelated healthy individuals from the same population carried this deletion. We excluded other disease-causing mutations in the coding regions of all genes within the linkage interval by sequencing; moreover, we verified the complete absence of a functional TUSC3 transcript in all patients through RT-PCR. TUSC3 is thought to encode a subunit of the endoplasmic reticulum-bound oligosaccharyltransferase complex that catalyzes a pivotal step in the protein N-glycosylation process. Our data suggest that in contrast to other genetic defects of glycosylation, inactivation of TUSC3 causes nonsyndromic MR, a conclusion that is supported by a separate report in this issue of AJHG. TUSC3 is only the fifth gene implicated in NS-ARMR and the first for which mutations have been reported in more than one family.
External Publication Status:published
Document Type:Article
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran 19834, Iran;
2.Kariminejad-Najmabadi Pathology & Genetics Center, Tehran 14667, Iran;
3.Medical Genetics Counselling Centre, Hamedan Welfare Organization, Hamedan 6516815353, Iran.
Identifiers:URL:http://www.cell.com/AJHG/abstract/S0002-9297(08)00...
DOI:10.1016/j.ajhg.2008.03.018
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