Supplementary Material for: Clinical and Molecular Heterogeneity in Brazilian Patients with Sotos Syndrome

Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by overgrowth, macrocephaly, distinctive facial features and variable degree of intellectual disability. Haploinsufficiency of the <i>NSD1</i> gene at 5q35.3, arising from 5q35 microdeletions, point mutations, and partial gene deletions, accounts for a majority of patients with SoS. Recently, mutations and possible pathogenetic rare CNVs, both affecting a few candidate genes for overgrowth, have been reported in patients with Sotos-like overgrowth features. To estimate the frequency of <i>NSD1</i> defects in the Brazilian SoS population and possibly reveal other genes implicated in the etiopathogenesis of this syndrome, we collected a cohort of 21 Brazilian patients, who fulfilled the diagnostic criteria for SoS, and analyzed the <i>NSD1</i> and <i>PTEN</i> genes by means of multiplex ligation-dependent probe amplification and mutational screening analyses. We identified a classical <i>NSD1</i> microdeletion, a novel missense mutation (p.C1593W), and 2 previously reported truncating mutations: p.R1984X and p.V1760Gfs*2. In addition, we identified a novel de novo <i>PTEN</i> gene mutation (p.D312Rfs*2) in a patient with a less severe presentation of SoS phenotype, which did not include pre- and postnatal overgrowth. For the first time, our study implies <i>PTEN</i> in the pathogenesis of SoS and further emphasizes the existence of ethno-geographical differences in <i>NSD1</i> molecular alterations between patients with SoS from Europe/North America (70-93%) and those from South America (10-19%).