dHPLC screening of the NSD1 gene identifies nine novel mutations--summary of the first 100 Sotos syndrome mutations.

Sotos syndrome belongs to the family of overgrowth syndromes and is characterized by large head circumference, craniofacial anomalies, advanced bone age and mental retardation. The syndrome is due to haploinsufficiency of the NSD1 gene, consisting of 23 exons with an open reading frame of 8088bp, which makes mutation screening by direct sequencing quite a laborious and expensive task. We have developed a dHPLC screening protocol for mutation detection in NSD1 and identified 9 novel mutations among 33 patients, thus achieving a mutation detection efficiency comparable to direct sequencing. A real-time quantitative PCR approach identified two patients with NSD1 deletions. Our mutation screen is compared to other studies and all published mutations and polymorphisms are summarized.