title: Clinical and molecular heterogeneity in brazilian patients with sotos syndrome.
abstract: 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%).
authors: J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, S.C., USA ; Department of Genetics, São Paulo State University, Botucatu, Rio de Janeiro, Brazil.
authors: Gustavo H
authors: GH
authors: Vieira
authors: J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, S.C., USA.
authors: Melissa M
authors: MM
authors: Cook
authors: Institute of Biology, Federal University of Bahia, Salvador, Rio de Janeiro, Brazil.
authors: Renata L
authors: RL
authors: Ferreira De Lima
authors: Department of Genetics, São Paulo State University, Botucatu, Rio de Janeiro, Brazil.
authors: Carlos E
authors: CE
authors: Frigério Domingues
authors: Department of Genetics, São Paulo State University, Botucatu, Rio de Janeiro, Brazil.
authors: Daniel R
authors: DR
authors: de Carvalho
authors: Department of Pediatrics, Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Isaias
authors: I
authors: Soares de Paiva
authors: Department of Genetics, São Paulo State University, Botucatu, Rio de Janeiro, Brazil.
authors: Danilo
authors: D
authors: Moretti-Ferreira
authors: J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, S.C., USA ; Department of Genetics and Biochemistry, Clemson University, Clemson, S.C., USA.
authors: Anand K
authors: AK
authors: Srivastava
keywords: Deletion; Mutation; NSD1; Overgrowth syndrome; PTEN; Sotos syndrome