title: Mutation analysis of the NSD1 gene in a group of 59 patients with congenital overgrowth.
abstract: Sotos syndrome is characterized by pre- and post-natal overgrowth, typical craniofacial features, advanced bone age, and developmental delay. Some degree of phenotypic overlap exists with other overgrowth syndromes, in particular with Weaver syndrome. Sotos syndrome is caused by haploinsufficiency of the NSD1 (nuclear receptor SET domain containing gene 1) gene. Microdeletions involving the gene are the major cause of the syndrome in Japanese patients, whereas intragenic mutations are more frequent in non-Japanese patients. NSD1 aberrations have also been described in some patients diagnosed as Weaver syndrome. Some authors have suggested a certain degree of genotype-phenotype correlation, with a milder degree of overgrowth, a more severe mental retardation, and a higher frequency of congenital anomalies in microdeleted patients. Data on larger series are needed to confirm this suggestion. We report here on microdeletion and mutation analysis of NSD1 in 59 patients with congenital overgrowth. Fourteen novel mutations, two previously described and one microdeletion were identified. All patients with a NSD1 mutation had been clinically classified as "classical Sotos," although their phenotype analysis demonstrated that some major criteria, such as overgrowth and macrocephaly, could be absent. All patients with confirmed mutations shared the typical Sotos facial gestalt. A high frequency of congenital heart defects was present in patients with intragenic mutations, supporting the relevance of the NSD1 gene in the pathogenesis of this particular defect.
authors.affiliation: SC Genetica Umana, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cecconi
authors.forename: F
authors.initials: F
authors.lastname: Forzano
authors.forename: D
authors.initials: D
authors.lastname: Milani
authors.forename: S
authors.initials: S
authors.lastname: Cavani
authors.forename: C
authors.initials: C
authors.lastname: Baldo
authors.forename: A
authors.initials: A
authors.lastname: Selicorni
authors.forename: C
authors.initials: C
authors.lastname: Pantaleoni
authors.forename: M
authors.initials: M
authors.lastname: Silengo
authors.forename: G B
authors.initials: GB
authors.lastname: Ferrero
authors.forename: G
authors.initials: G
authors.lastname: Scarano
authors.forename: M
authors.initials: M
authors.lastname: Della Monica
authors.forename: R
authors.initials: R
authors.lastname: Fischetto
authors.forename: P
authors.initials: P
authors.lastname: Grammatico
authors.forename: S
authors.initials: S
authors.lastname: Majore
authors.forename: G
authors.initials: G
authors.lastname: Zampino
authors.forename: L
authors.initials: L
authors.lastname: Memo
authors.forename: E Lucci
authors.initials: EL
authors.lastname: Cordisco
authors.forename: G
authors.initials: G
authors.lastname: Neri
authors.forename: M
authors.initials: M
authors.lastname: Pierluigi
authors.forename: F Dagna
authors.initials: FD
authors.lastname: Bricarelli
authors.forename: M
authors.initials: M
authors.lastname: Grasso
authors.forename: Francesca
authors.initials: F
authors.lastname: Faravelli
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006130:Growth Disorders / Q000151:congenital / Q000235:genetics*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D013577:Syndrome
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human