Identification of a novel de novo nonsense mutation of the NSD1 gene in monozygotic twins discordant for Sotos syndrome

Introduction Sotos syndrome is a congenital overgrowth disorder characterized by facial gestalt, excessively rapid growth, acromegalic features and a non-progressive cerebral disorder with intellectual disability. Methodology The identical male twins showed somewhat different clinical, cognitive and behavioural phenotypes. Abnormal clinical manifestations including seizures, scoliosis, enlarged ventricles, and attention-deficit/hyperactivity disorder (ADHD) were found in the proband (first twin), but not in the sibling (second twin). We used diagnostic exome sequencing (DES) to identify a heterozygous de novo mutation of the NSD1 gene in monozygotic twins with Sotos syndrome. Results DES revealed a novel nonsense mutation c.2596G > T (p.Glu866*) of the NSD1 gene in the proband, the first of monozygotic twins. Sanger sequencing analysis of the proband and his family members showed that this nonsense mutation was present in the proband and his sibling, but was absent in their parents, indicating that it occurred with de novo origin. Conclusion This finding expands the phenotypic spectrum associated with variable expression of the Sotos syndrome caused by NSD1 mutation, and it adds further support for postconceptual mutation, epigenetic change and/or an environmental factor involved in the cause of the Sotos syndrome.