Molecular Basis of Sotos SyndromeNiikawa N.
aDepartment of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki; bCREST, Japan Science and Technology Agency, Kawaguchi, Japan
This paper describes the isolation of a novel human gene, NSD1, from the 5q35 breakpoint of t(5;8)(q35; q24.1) in a patient with Sotos syndrome, and NSD1 mutation analysis. Of 112 (95 Japanese and 17 non-Japanese) patients analyzed, 16 (14%) had a heterozygous NSD1 point mutation (10 protein truncation types and six missense types) and 50 (45%) a ∼0.7-Mb microdeletion involving NSD1. The results indicated that haploinsufficiency of NSD1 is the major cause of Sotos syndrome, and NSD1 plays a role in growth and brain development in humans. Detailed clinical examinations provided a genotype-phenotype correlation in Sotos syndrome, i.e. in patients with deletions, overgrowth is less obvious and mental retardation is more severe than in those with point mutations, and major anomalies were exclusively seen in the former. The results also indicated that Sotos syndrome due to a deletion falls into a contiguous gene syndrome, while Sotos syndrome due to an NSD1 point mutation is a single gene defect, occasionally with an autosomal dominant mode of inheritance. The genomic structure around the deleted and flanking regions revealed the presence of two sets of low copy repeats through which the microdeletion in Sotos syndrome is mediated.
Dr. Norio Niikawa
Department of Human Genetics
Nagasaki University Graduate School of Biomedical Sciences
Sakamoto 1-12-4, Nagasaki 852-8523 (Japan)
Tel. +81 95 8497118, Fax +81 95 8497121, E-Mail firstname.lastname@example.org
Number of Print Pages : 6
Number of Figures : 5, Number of Tables : 2, Number of References : 19
Hormone Research (From Development Endocrinology to Clinical Research)
Vol. 62, No. Suppl. 3, Year 2004 (Cover Date: Released October 2004)
Journal Editor: P. Czernichow, Paris
ISSN: 0301–0163 (print), 1423–0046 (Online)
For additional information: http://www.karger.com/hre