PMID- 21108392
OWN - NLM
STAT- MEDLINE
DCOM- 20110315
LR  - 20211020
IS  - 1552-4833 (Electronic)
IS  - 1552-4825 (Print)
IS  - 1552-4825 (Linking)
VI  - 152A
IP  - 12
DP  - 2010 Dec
TI  - Recurrent interstitial 1p36 deletions: Evidence for germline mosaicism and 
      complex rearrangement breakpoints.
PG  - 3074-83
LID - 10.1002/ajmg.a.33733 [doi]
AB  - Deletions of chromosome 1p36 are one of the most frequently encountered 
      subtelomeric alterations. Clinical features of monosomy 1p36 include 
      neurocognitive impairment, hearing loss, seizures, cardiac defects, and 
      characteristic facial features. The majority of cases have occurred sporadically, 
      implying that genomic instability plays a role in the prevalence of the syndrome. 
      Here, we report two siblings with mild phenotypic features of the deletion 
      syndrome, including developmental delay, hearing loss, and left ventricular 
      non-compaction (LVNC). Microarray analysis using bacterial artificial chromosome 
      and oligonucleotide microarrays indicated the deletions were identical, 
      suggesting germline mosaicism. Parental phenotypes were normal, and analysis by 
      fluorescence in situ hybridization (FISH) did not show mosaicism. These small 
      interstitial deletions were not detectable by conventional subtelomeric FISH 
      analysis. To investigate the mechanism of deletion further, the breakpoints were 
      cloned and sequenced, demonstrating the presence of a complex rearrangement. 
      Sequence analysis of genes in the deletion interval did not reveal any mutations 
      on the intact homologue that may have contributed to the LVNC seen in both 
      children. This is the first report of apparent germline mosaicism for this 
      disorder. Thus, our findings have important implications for diagnostic 
      approaches and for recurrence risk counseling in families with a child with 
      monosomy 1p36. In addition, our results further refine the minimal critical 
      region for LVNC and hearing loss.
CI  - (c) 2010 Wiley-Liss, Inc.
FAU - Gajecka, Marzena
AU  - Gajecka M
AD  - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
FAU - Saitta, Sulagna C
AU  - Saitta SC
FAU - Gentles, Andrew J
AU  - Gentles AJ
FAU - Campbell, Lindsey
AU  - Campbell L
FAU - Ciprero, Karen
AU  - Ciprero K
FAU - Geiger, Elizabeth
AU  - Geiger E
FAU - Catherwood, Anne
AU  - Catherwood A
FAU - Rosenfeld, Jill A
AU  - Rosenfeld JA
FAU - Shaikh, Tamim
AU  - Shaikh T
FAU - Shaffer, Lisa G
AU  - Shaffer LG
LA  - eng
GR  - R01 GM081519/GM/NIGMS NIH HHS/United States
GR  - R01 GM081519-01/GM/NIGMS NIH HHS/United States
GR  - GM081519/GM/NIGMS NIH HHS/United States
PT  - Case Reports
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Abnormalities, Multiple/diagnosis/genetics
MH  - Child, Preschool
MH  - *Chromosome Breakage
MH  - Chromosomes, Artificial, Bacterial/genetics
MH  - *Chromosomes, Human, Pair 1
MH  - Comparative Genomic Hybridization
MH  - DNA/genetics
MH  - Developmental Disabilities/genetics
MH  - Female
MH  - Gene Rearrangement/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Microarray Analysis
MH  - Monosomy
MH  - *Mosaicism
MH  - Oligonucleotide Array Sequence Analysis
MH  - *Sequence Deletion
MH  - Syndrome
PMC - PMC3058890
MID - NIHMS237251
EDAT- 2010/11/26 06:00
MHDA- 2011/03/16 06:00
PMCR- 2011/12/01
CRDT- 2010/11/26 06:00
PHST- 2010/11/26 06:00 [entrez]
PHST- 2010/11/26 06:00 [pubmed]
PHST- 2011/03/16 06:00 [medline]
PHST- 2011/12/01 00:00 [pmc-release]
AID - 10.1002/ajmg.a.33733 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2010 Dec;152A(12):3074-83. doi: 10.1002/ajmg.a.33733.