PMID- 25339188
OWN - NLM
STAT- MEDLINE
DCOM- 20150819
LR  - 20200930
IS  - 1552-4833 (Electronic)
IS  - 1552-4825 (Linking)
VI  - 167A
IP  - 1
DP  - 2015 Jan
TI  - Complex de novo chromosomal rearrangement at 15q11-q13 involving an 
      intrachromosomal triplication in a patient with a severe neuropsychological 
      phenotype: clinical report and review of the literature.
PG  - 221-30
LID - 10.1002/ajmg.a.36815 [doi]
AB  - Interstitial triplications of 15q11-q13, leading to tetrasomy of the involved 
      region, are very rare, with only 11 cases reported to date. Their pathogenicity 
      is independent of the parental origin of the rearranged chromosome. The 
      associated phenotype resembles, but is less severe, than that of patients bearing 
      inv dup(15) marker chromosomes. Here, we describe a boy of 3 years and 9 months 
      of age who exhibited very mild craniofacial dysmorphism (arched eyebrows, 
      hypertelorism, and a wide mouth), developmental delay, generalized hypotonia, 
      ataxic gait, severe intellectual disability, and autism. Array comparative 
      genomic hybridization (CGH) analysis identified a heterozygous duplication of 
      1.1 Mb at 15q11.2 (between low-copy repeats BP1 and BP2), and a heterozygous 
      triplication of 6.8 Mb at 15q11.2-q13.1 (BP2-BP4). Both acquisitions were de novo 
      and contiguous. Microsatellite polymorphism analysis revealed the maternal origin 
      of the triplication and the involvement of both maternal chromosomes 15. 
      Furthermore, fluorescence in situ hybridization (FISH) analysis using BAC clones 
      revealed that the rearrangement was complex, containing three differently sized 
      tandem repeats of which the middle one was inverted. Our study confirms and 
      extends the model proposed to explain the formation of intrachromosomal 
      triplications through recombination events between non-allelic duplicons. The 
      comparison of the proband's clinical presentation with those of previously 
      described cases attests the existence of endophenotypes due to the parental 
      origin of the 15q11-q13 triplicated segment and suggests a timetable for 
      achievement of developmental milestones, thereby contributing to improved 
      genotype-phenotype correlations.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Castronovo, Chiara
AU  - Castronovo C
AD  - Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto 
      Auxologico Italiano, Milano, Italy.
FAU - Crippa, Milena
AU  - Crippa M
FAU - Bestetti, Ilaria
AU  - Bestetti I
FAU - Rusconi, Daniela
AU  - Rusconi D
FAU - Russo, Silvia
AU  - Russo S
FAU - Larizza, Lidia
AU  - Larizza L
FAU - Sangermani, Roberto
AU  - Sangermani R
FAU - Bonati, Maria Teresa
AU  - Bonati MT
FAU - Finelli, Palma
AU  - Finelli P
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20141022
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
RN  - 0 (SNRPN protein, human)
RN  - 0 (snRNP Core Proteins)
SB  - IM
MH  - Adult
MH  - Child, Preschool
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human, Pair 15/*genetics
MH  - Comparative Genomic Hybridization
MH  - Facies
MH  - Female
MH  - Gene Rearrangement/*genetics
MH  - Genetic Loci
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Mental Disorders/*genetics
MH  - Phenotype
MH  - Trisomy/*genetics
MH  - snRNP Core Proteins/genetics
OTO - NOTNLM
OT  - 15q11-q13 interstitial triplications
OT  - NAHR
OT  - U-type exchange
OT  - array CGH
OT  - autism
OT  - low-copy repeat
EDAT- 2014/10/24 06:00
MHDA- 2015/08/20 06:00
CRDT- 2014/10/24 06:00
PHST- 2013/12/11 00:00 [received]
PHST- 2014/09/12 00:00 [accepted]
PHST- 2014/10/24 06:00 [entrez]
PHST- 2014/10/24 06:00 [pubmed]
PHST- 2015/08/20 06:00 [medline]
AID - 10.1002/ajmg.a.36815 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2015 Jan;167A(1):221-30. doi: 10.1002/ajmg.a.36815. Epub 2014 
      Oct 22.