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 NSD1 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 NSD1 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 NSD1 and PTEN genes by means of multiplex 
ligation-dependent probe amplification and mutational screening analyses. We 
identified a classical NSD1 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 PTEN 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 PTEN in the 
pathogenesis of SoS and further emphasizes the existence of ethno-geographical 
differences in NSD1 molecular alterations between patients with SoS from 
Europe/North America (70-93%) and those from South America (10-19%).