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          Institute: MPI für molekulare Genetik     Collection: Research Group Development and Disease     Display Documents



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ID: 175489.0, MPI für molekulare Genetik / Research Group Development and Disease
Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes
Authors:Tuerkmen, Seval; Gillessen-Kaesbach, Gabriele; Meinecke, Peter; Albrecht, Beate; Neumann, Luitgard M.; Hesse, Volker; Palanduz, Suekrue; Balg, Stefanie; Majewski, Frank; Fuchs, Sigrun; Zschieschang, Petra; Greiwe, Monika; Mennicke, Kirsteen; Kreuz, Friedmar R.; Dehmel, Harald J.; Rodeck, Burkhard; Kunze, Juergen; Tinschert, Sigrid; Mundlos, Stefan; Horn, Denise
Language:English
Date of Publication (YYYY-MM-DD):2003-11
Title of Journal:European Journal of Human Genetics
Journal Abbrev.:Eur. J. Hum. Genet.
Volume:11
Issue / Number:11
Start Page:858
End Page:865
Copyright:© 2003 Nature Publishing Group
Review Status:not specified
Audience:Experts Only
Abstract / Description:Recently, deletions encompassing the nuclear receptor binding SET-Domain 1 (NSD1) gene have been described as the major cause of Japanese patients with the Sotos syndrome, whereas point mutations have been identified in the majority of European Sotos syndrome patients. In order to investigate a possible phenotype-genotype correlation and to further define the predictive value of NSD1 mutations, we performed mutational analysis of the NSD1 gene in 20 patients and one familial case with Sotos syndrome, five patients with Weaver syndrome, six patients with unclassified overgrowth/mental retardation, and six patients with macrocephaly/mental retardation. We were able to identify mutations within the NSD1 gene in 18 patients and the familial case with Sotos syndrome (90%). The mutations (six nonsense, eight frame shifts, three splice site, one missense, one in-frame deletion) are expected to result in an impairment of NSD1 function. The best correlation between clinical assessment and molecular results was obtained for the Sotos facial gestalt in conjunction with overgrowth, macrocephaly, and developmental delay. In contrast to the high mutation detection rate in Sotos syndrome, none of the patients with Weaver syndrome, unclassified overgrowth/mental retardation and macrocephaly/mental retardation, harbored NSD1 mutations. We tested for large deletions by FISH analysis but were not able to identify any deletion cases. The results indicate that the great majority of patients with Sotos syndrome are caused by mutations in NSD1. Deletions covering the NSD1 locus were not found in the patients analyzed here.
Free Keywords:NSD1, Sotos syndrome, Weaver syndrome, direct sequencing, FISH
Comment of the Author/Creator:Date: 2003, NOV
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Stefan Mundlos
Affiliations:MPI für molekulare Genetik
External Affiliations:Humboldt Univ, Charite, Inst Med Genet, D-13353 Berlin, Germany.; Max Planck Inst Mol Genet, Berlin, Germany.; Univ Klinikum Essen, Inst Humangenet, Essen, Germany.; Altonaer Kinderkrankenhaus, Abt Med Genet, Hamburg, Germany.; Humboldt Univ, Charite, Inst Humangenet, Berlin, Germany.; Krankenhaus Lichtenberg, Klin Kinder & Jugendmed, Berlin, Germany.; Istanbul Univ, Dept Internal Med, Div Med Genet, Istanbul, Turkey.; Kinderzentrum Muenchen, Munich, Germany.; Univ Duesseldorf, Inst Humangenet & Anthropol, D-4000 Duesseldorf, Germany.; Univ Frankfurt Klinikum, Inst Humangenet, D-6000 Frankfurt, Germany.; Univ Klinikum Luebeck, Inst Humangenet, Luebeck, Germany.; Tech Univ Dresden, Inst Klin Genet, D-8027 Dresden, Germany.; Kinderaerztliche Gemeinschaftpraxis, Bremen, Germany.; Marien Hosp, Klin Kinderheilkunde & Jugendmed, Osnabrueck, Germany.
Identifiers:ISI:000186074200007 [ID No:1]
ISSN:1018-4813 [ID No:2]
DOI:10.1038/sj.ejhg.5201050 [ID No:3]
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