Two cases of Sotos syndrome with novel mutations of the NSD1 gene.

Mutations and deletions of the NSD1 gene, located on chromosome 5q35, are responsible for over 90% of cases of Sotos syndrome. Fluorescent in situ hybridization analysis (FISH), MLPA or multiplex quantitative PCR allow detection of total/partial NSD1 deletions and direct sequencing allows detection of NSD1 mutations. We describe two boys with Sotos syndrome in whom PCR amplification and direct sequencing of the NSD1 gene identified two novel mutations not previously described: c.4736dupG in exon 12 and c.3938_3939insT in exon 7. In addition to the cardinal and major features of the syndrome (abnormal facial appearance, overgrowth, cardiac anomalies, renal anomalies, hypotonia, neonatal jaundice, seizures and brain MRI abnormalities) in both patients, one boy also had cryptorchidism and vertebral anomalies, features considered not common. Despite the wide range of possible combinations of phenotypic features, molecular analysis can correctly identify Sotos syndrome.