title: MLPA analysis in 30 Sotos syndrome patients revealed one total NSD1 deletion and two partial deletions not previously reported.
abstract: Sotos syndrome (MIM #117550) is an autosomal dominant condition characterized by pre and postnatal overgrowth, macrocephaly and typical facial gestalt with frontal bossing, hypertelorism, antimongoloid slant of the palpebral fissures, prominent jaw and high and narrow palate. This syndrome is also frequently associated with brain, cardiovascular, and urinary anomalies and is occasionally accompanied by malignant lesions such as Wilms tumour and hepatocarcinoma. The syndrome is known to be caused by mutations or deletions of the NSD1 gene. To detect both 5q35 microdeletions and partial NSD1 gene deletions we screened 30 Brazilian patients with clinical diagnosis of Sotos syndrome by multiplex ligation dependent probe amplification. We identified one patient with a total deletion of NSD1 and neighbouring FGFR4, other with missing NSD1 exons 13-14 and another with a deletion involving FGFR4 and spanning up to NSD1 exon 17. All deletions were de novo. The two NSD1 partial deletions have not been previously reported. The clinical features of the three patients included a typical facial gestalt with frontal bossing, prominent jaw and high anterior hairline; macrocephaly, dolichocephaly, large hands; neonatal hypotonia and jaundice. All presented normal growth at birth but postnatal overgrowth. Two patients with NSD1 and FGFR4 gene deletions presented congenital heart anomalies.
authors: Center for Human Genome Research, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil. claufagali@hotmail.com
authors: Claudia
authors: C
authors: Fagali
authors: Fernando
authors: F
authors: Kok
authors: Pablo
authors: P
authors: Nicola
authors: Chong
authors: C
authors: Kim
authors: Débora
authors: D
authors: Bertola
authors: Lílian
authors: L
authors: Albano
authors: Célia P
authors: CP
authors: Koiffmann
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D002895:Chromosomes, Human, Pair 5; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D002658:Developmental Disabilities / Q000235:genetics; D005091:Exons; D019066:Facies; D005260:Female; D006130:Growth Disorders / Q000235:genetics*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D017384:Sequence Deletion; D013577:Syndrome
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D004247:DNA; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human