Abstract:

Objective Molecular diagnosis was performed for 2 suspected cases of Sotos syndrome. To seek the cause of disease and make a definite clinical diagnosis,and to analyze the relationship between genotype and phenotype. Methods Totally,2 children came from the Medical Genetics Department of Shanghai Children's Medical Center,who mainly presented overgrowth,developmental delay,macrocephaly and typical facial appearance. They accepted chromosomal microarray analysis and gene panel test,respectively. Literature review was performed to get to know the relationship between genotype and phenotype. Results A heterozygous microdeletion of 1 907 kb in 5q35.2-q35.3 was found in 1 case by chromosomal microarray analysis,which contained NSD1 gene. This case was confirmed as Sotos syndrome of 5q35 microdeletion. Another case showed a heterozygous nonsense mutation of c.1262G>A,p.Trp421* in NSD1 gene. This case was diagnosed as Sotos syndrome of NSD1 intragenic mutation. Pooled analysis about the features of genotype and phenotype was performed in all 5 inland Chinese cases,which helped us with understanding the relationship between genotype and phenotype. Conclusions NSD1 gene variation causes Sotos syndrome. There is a high relationship between the variety of clinical features and the heterogeneity of NSD1 gene alteration. Gene tests are useful to improve the rate of clinical diagnosis for such rare genetic disease.

Key words: Sotos syndrome, NSD1 gene, Variation, Phenotype, Gene sequencing