PMID- 11788094
OWN - NLM
STAT- MEDLINE
DCOM- 20020327
LR  - 20061115
IS  - 1090-6576 (Print)
IS  - 1090-6576 (Linking)
VI  - 5
IP  - 3
DP  - 2001 Fall
TI  - Gene dosage analysis in Silver-Russell syndrome: use of quantitative competitive 
      PCR and dual-color FISH to estimate the frequency of duplications in 7p11.2-p13.
PG  - 261-6
AB  - Silver-Russell syndrome (SRS) describes a heterogeneous malformation syndrome 
      mainly characterized by intrauterine and postnatal growth retardation 
      (IUGR/PNGR). Approximately 10% of SRS cases have been associated with maternal 
      uniparental disomy (matUPD) 7. This suggests the involvement of at least one 
      imprinted gene on chromosome 7 in the pathogenesis of SRS. Additionally, two 
      familial and one single SRS patients have been published with an interstitial 
      duplication in 7p11.2-p13, including the genes GRB10 and IGFBP1; IGFBP3 was 
      investigated in only one case revealing duplication; conversely, double gene 
      dosage of EGFR was excluded in all 3 patients. Two further cytogenetically 
      abnormal cases, one with a paracentric inversion (7)(p14p12) and one with 
      matUPD7/partial trisomy for 7p13-q11, confirmed that the proximal short arm of 
      chromosome represents an interesting region possibly harboring (a) candidate 
      gene(s) for SRS. Although previously published investigations on the genes GRB10, 
      IGFBP1, IGFBP3, and EGFR report neither disease-relevant mutations nor abnormal 
      imprinting patterns, the SRS cases with chromosomal duplications suggest that 
      variation of gene copy number might be a further type of mutation. To obtain 
      meaningful results on the frequency of duplications in proximal 7p, we screened 
      32 SRS patients using quantitative PCR assays for GRB10, IGFBP1, IGFBP3, and 
      EGFR. The data were confirmed by dual-color fluorescence in situ hybridization 
      (FISH) of spot check samples. Results obtained by both methods exclude 
      duplications in all analyzed patients and indicate an overall percentage of 
      duplication among SRS patients between 2.4% (GRB10) and 5% (IGFBP1). By testing 
      and evaluating quantitative competitive PCR for various loci, we developed a 
      practical approach for gene dosage analysis which can be easily established for 
      routine purposes.
FAU - Mergenthaler, S
AU  - Mergenthaler S
AD  - Institute of Human Genetics, Technical University of Aachen, Pauwelsstrasse 30, 
      D-52074 Aachen, Germany.
FAU - Sharp, A
AU  - Sharp A
FAU - Ranke, M B
AU  - Ranke MB
FAU - Kalscheuer, V M
AU  - Kalscheuer VM
FAU - Wollmann, H A
AU  - Wollmann HA
FAU - Eggermann, T
AU  - Eggermann T
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genet Test
JT  - Genetic testing
JID - 9802546
SB  - IM
MH  - Cell Nucleus/ultrastructure
MH  - *Chromosomes, Human, Pair 7/physiology
MH  - Fetal Growth Retardation
MH  - *Gene Dosage
MH  - *Gene Duplication
MH  - Gene Frequency
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Interphase
MH  - Lymphocytes
MH  - Polymerase Chain Reaction/*methods
EDAT- 2002/01/15 10:00
MHDA- 2002/03/28 10:01
CRDT- 2002/01/15 10:00
PHST- 2002/01/15 10:00 [pubmed]
PHST- 2002/03/28 10:01 [medline]
PHST- 2002/01/15 10:00 [entrez]
AID - 10.1089/10906570152742335 [doi]
PST - ppublish
SO  - Genet Test. 2001 Fall;5(3):261-6. doi: 10.1089/10906570152742335.