ONLINE MUTATION REPORT Identification of eight novel NSD1 mutations in Sotos

otos syndrome or cerebral gigantism (SoS, OMIM #117550) is a well-known disorder characterised by overgrowth with advanced bone age, craniofacial anomalies, developmental delay, and occasional seizures.1 2 A typical face has a large head circumference, frontal bossing with high anterior hairline, down slanting of palpebral fissures, flat nasal bridge, and prominent jaw.3 The hands and feet are usually large. Height and weight tends to normalise in adulthood.4 EEG abnormalities, hypotonia, strabismus, congenital heart defects, kyphoscoliosis, and cancer have also been noted.3 5–10 Since the original report in 1964,1 more than 300 affected cases have been reported. Most cases are sporadic, while several familial cases have been described, suggesting that SoS is an autosomal dominant disorder.8 11–17 We have previously isolated the nuclear receptor SET domain containing gene 1 (NSD1) from the 5q35 transloca-tion breakpoint in a Japanese SoS patient with t(5;8)(q35; q24.1).18 19 NSD1 encodes 2696 amino acids (GenBank accession no. AF395588), and the gene has several putativ