PMID- 11685205
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20240312
IS  - 1061-4036 (Print)
IS  - 1546-1718 (Electronic)
IS  - 1061-4036 (Linking)
VI  - 29
IP  - 3
DP  - 2001 Nov
TI  - A 1.5 million-base pair inversion polymorphism in families with Williams-Beuren 
      syndrome.
PG  - 321-5
AB  - Williams-Beuren syndrome (WBS) is most often caused by hemizygous deletion of a 
      1.5-Mb interval encompassing at least 17 genes at 7q11.23 (refs. 1,2). As with 
      many other haploinsufficiency diseases, the mechanism underlying the WBS deletion 
      is thought to be unequal meiotic recombination, probably mediated by the highly 
      homologous DNA that flanks the commonly deleted region. Here, we report the use 
      of interphase fluorescence in situ hybridization (FISH) and pulsed-field gel 
      electrophoresis (PFGE) to identify a genomic polymorphism in families with WBS, 
      consisting of an inversion of the WBS region. We have observed that the inversion 
      is hemizygous in 3 of 11 (27%) atypical affected individuals who show a subset of 
      the WBS phenotypic spectrum but do not carry the typical WBS microdeletion. Two 
      of these individuals also have a parent who carries the inversion. In addition, 
      in 4 of 12 (33%) families with a proband carrying the WBS deletion, we observed 
      the inversion exclusively in the parent transmitting the disease-related 
      chromosome. These results suggest the presence of a newly identified genomic 
      variant within the population that may be associated with the disease. It may 
      result in predisposition to primarily WBS-causing microdeletions, but may also 
      cause translocations and inversions.
FAU - Osborne, L R
AU  - Osborne LR
AD  - Department of Medicine, The University of Toronto, 1 King's College Circle, 
      Toronto, Ontario, Canada.
FAU - Li, M
AU  - Li M
FAU - Pober, B
AU  - Pober B
FAU - Chitayat, D
AU  - Chitayat D
FAU - Bodurtha, J
AU  - Bodurtha J
FAU - Mandel, A
AU  - Mandel A
FAU - Costa, T
AU  - Costa T
FAU - Grebe, T
AU  - Grebe T
FAU - Cox, S
AU  - Cox S
FAU - Tsui, L C
AU  - Tsui LC
FAU - Scherer, S W
AU  - Scherer SW
LA  - eng
SI  - GENBANK/AF020782
SI  - GENBANK/AZ757825
SI  - GENBANK/AZ757826
SI  - GENBANK/G68161
SI  - GENBANK/G68162
SI  - GENBANK/G68163
SI  - GENBANK/G68164
GR  - 38103/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Genetic Markers)
SB  - IM
MH  - Adolescent
MH  - *Chromosome Inversion
MH  - Chromosomes, Human, Pair 7/genetics
MH  - Electrophoresis, Gel, Pulsed-Field
MH  - Female
MH  - Genetic Markers/genetics
MH  - Genetic Predisposition to Disease/genetics
MH  - Genotype
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Male
MH  - Molecular Sequence Data
MH  - Mutation/genetics
MH  - Phenotype
MH  - Physical Chromosome Mapping
MH  - Polymorphism, Genetic/*genetics
MH  - Williams Syndrome/*genetics
PMC - PMC2889916
MID - CAMS401
OID - NLM: CAMS401
EDAT- 2001/10/31 10:00
MHDA- 2002/01/05 10:01
PMCR- 2010/06/22
CRDT- 2001/10/31 10:00
PHST- 2001/10/31 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/31 10:00 [entrez]
PHST- 2010/06/22 00:00 [pmc-release]
AID - ng753 [pii]
AID - 10.1038/ng753 [doi]
PST - ppublish
SO  - Nat Genet. 2001 Nov;29(3):321-5. doi: 10.1038/ng753.