PMID- 23341071
OWN - NLM
STAT- MEDLINE
DCOM- 20130805
LR  - 20201209
IS  - 1552-4833 (Electronic)
IS  - 1552-4825 (Linking)
VI  - 161A
IP  - 3
DP  - 2013 Mar
TI  - A novel mosaic NSD1 intragenic deletion in a patient with an atypical phenotype.
PG  - 611-8
LID - 10.1002/ajmg.a.35814 [doi]
AB  - 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.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Castronovo, Chiara
AU  - Castronovo C
AD  - Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto 
      Auxologico Italiano, Milano, Italy. c.castronovo@auxologico.it
FAU - Rusconi, Daniela
AU  - Rusconi D
FAU - Crippa, Milena
AU  - Crippa M
FAU - Giardino, Daniela
AU  - Giardino D
FAU - Gervasini, Cristina
AU  - Gervasini C
FAU - Milani, Donatella
AU  - Milani D
FAU - Cereda, Anna
AU  - Cereda A
FAU - Larizza, Lidia
AU  - Larizza L
FAU - Selicorni, Angelo
AU  - Selicorni A
FAU - Finelli, Palma
AU  - Finelli P
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130122
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nuclear Proteins)
RN  - EC 2.1.1.- (Histone Methyltransferases)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.1.1.43 (NSD1 protein, human)
SB  - IM
MH  - Abnormalities, Multiple/*diagnosis/genetics
MH  - Child, Preschool
MH  - Comparative Genomic Hybridization
MH  - Developmental Disabilities/*diagnosis/genetics
MH  - Heterozygote
MH  - Histone Methyltransferases
MH  - Histone-Lysine N-Methyltransferase
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*genetics
MH  - Male
MH  - Molecular Diagnostic Techniques
MH  - Mosaicism
MH  - Nuclear Proteins/*genetics
MH  - Phenotype
MH  - Sequence Deletion
EDAT- 2013/01/24 06:00
MHDA- 2013/08/06 06:00
CRDT- 2013/01/24 06:00
PHST- 2011/09/07 00:00 [received]
PHST- 2012/11/14 00:00 [accepted]
PHST- 2013/01/24 06:00 [entrez]
PHST- 2013/01/24 06:00 [pubmed]
PHST- 2013/08/06 06:00 [medline]
AID - 10.1002/ajmg.a.35814 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2013 Mar;161A(3):611-8. doi: 10.1002/ajmg.a.35814. Epub 2013 
      Jan 22.