Spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome.
BACKGROUND
Sotos syndrome is an overgrowth syndrome with characteristic facial gestalt and mental retardation of variable severity. Haploinsufficiency of the NSD1 gene has been implicated as the major cause of Sotos syndrome, with a predominance of microdeletions reported in Japanese patients. This study was conducted to investigate into the spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome.


METHODS
Thirty-six Chinese patients with Sotos syndrome and two patients with Weaver syndrome were subject to molecular testing.


RESULTS
NSD1 gene mutations were detected in 26 (72%) Sotos patients. Microdeletion was found in only 3 patients, while the other 23 had point mutations (6 frameshift, 8 nonsense, 2 spice site, and 7 missense). Of these, 19 mutations were never reported. NSD1 gene mutations were not found in the two patients with Weaver syndrome.


CONCLUSIONS
Most cases of Sotos syndrome are caused by NSD1 gene defects, but the spectrum of mutations is different from that of Japanese patients. Genotype-phenotype correlation showed that patients with microdeletions might be more prone to congenital heart disease but less likely to have somatic overgrowth. The two patients with Weaver syndrome were not found to have NSD1 gene mutations, but the number was too small for any conclusion to be drawn.
Tong
Tony M F
TM
Clinical Genetic Service, Department of Health, Hong Kong SAR, China. so_cg@dh.gov.hk
Hau
Edgar W L
EW
Lo
Ivan F M
IF
Chan
Daniel H C
DH
Lam
Stephen T S
ST
D000015:Abnormalities, Multiple / Q000235:genetics*; D001921:Brain / Q000002:abnormalities; D002675:Child, Preschool; D019465:Craniofacial Abnormalities / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D017353:Gene Deletion; D006130:Growth Disorders / Q000235:genetics*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D013577:Syndrome
D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human