title: A novel mosaic NSD1 intragenic deletion in a patient with an atypical phenotype.
abstract: Sotos syndrome, which is characterized by overgrowth, macrocephaly, distinctive facial features, and developmental delay, arises from mutations and deletions of the NSD1 gene at 5q35.3. Sixteen NSD1 intragenic deletions (including one in a mosaic condition) and one partial duplication have been reported in patients with Sotos syndrome. Here, we describe a boy aged 4 years and 10 months that showed facial dysmorphism (including frontal bossing, widely spaced eyes, deeply set eyes, a wide nasal bridge, anteverted nares, and a wide mouth), normal growth, and a psychomotor delay. High-resolution array comparative genomic hybridization (CGH) analysis identified a mosaic heterozygous intragenic NSD1 deletion of 38 kb, which included part of intron 2 and the entire exon 3, and led to NSD1 haploinsufficiency. The deletion somatic mosaicism was subsequently confirmed by fluorescence in situ hybridization (FISH) analysis using fosmid clones. This patient presents the most atypical phenotype thus far associated with NSD1 haploinsufficiency. It is possible that this atypical phenotype may have resulted from the somatic mosaicism of the NSD1 defect. Our study confirms the usefulness of array CGH for increasing the detection rate of NSD1 abnormalities and for diagnosing syndromic patients that do not present an easily recognized phenotype.
authors: Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milano, Italy. c.castronovo@auxologico.it
authors: Chiara
authors: C
authors: Castronovo
authors: Daniela
authors: D
authors: Rusconi
authors: Milena
authors: M
authors: Crippa
authors: Daniela
authors: D
authors: Giardino
authors: Cristina
authors: C
authors: Gervasini
authors: Donatella
authors: D
authors: Milani
authors: Anna
authors: A
authors: Cereda
authors: Lidia
authors: L
authors: Larizza
authors: Angelo
authors: A
authors: Selicorni
authors: Palma
authors: P
authors: Finelli
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000235:genetics; D006579:Heterozygote; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D025202:Molecular Diagnostic Techniques; D009030:Mosaicism; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D017384:Sequence Deletion
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human