title: Analysis of the NSD1 promoter region in patients with a Sotos syndrome phenotype.
abstract: Sotos syndrome (SoS, OMIM#117550) is an overgrowth disorder characterized by excessive growth-especially in the first years of childhood-distinctive craniofacial features, and various degrees of mental retardation. Haploinsufficiency of the nuclear receptor binding SET domain containing protein 1 (NSD1) gene, due to either intragenic mutations or whole-gene microdeletions, is found in the majority of patients with SoS. However, in approximately 10-40% of patients with a typical SoS phenotype, no abnormalities are detected. In this study, hemizygous hypermethylation or genomic sequence abnormalities of the promoter region of NSD1 were hypothesized to be the underlying cause in patients with a SoS phenotype, but without confirmed NSD1 alterations. In 18 patients, including one patient with a reported hepatocellular carcinoma, the promoter region of NSD1 was analyzed. However, no hypermethylation or sequence abnormalities in the promoter region could be detected. It therefore seems unlikely that such abnormalities of NSD1 are a major culprit in patients with phenotypical SoS. Additional methods are necessary for detection of other genetic or epigenetic causes of SoS.
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.|Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.|International Consortium for Medical Care of Hibakusha and Radiation Life Science, The 21st Century Center of Excellence, Nagasaki, Japan.
authors.forename: Remco
authors.initials: R
authors.lastname: Visser
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.|International Consortium for Medical Care of Hibakusha and Radiation Life Science, The 21st Century Center of Excellence, Nagasaki, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Niikawa
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. naomat@yokohama-cu.ac.jp.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan. naomat@yokohama-cu.ac.jp.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D001483:Base Sequence; D019175:DNA Methylation; D017931:DNA Primers; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013577:Syndrome
chemical_list: D017931:DNA Primers