Simpson-Golabi-Behmel syndrome: genotype/phenotype analysis of 18 affected males from 7 unrelated families.
Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth disorder recently shown to be caused by mutations in the heparan sulfate proteoglycan GPC3 [Pilia et al., Nat Genet; 12:241-247 1996]. We have used Southern blot analysis and polymerase chain reaction amplification of intra-exonic sequences to identify four new GPC3 mutations and further characterize three previously reported SGBS mutations. De novo GPC3 mutations were identified in 2 families. In general, the mutations were unique deletions ranging from less than 0.1 kb to more than 300 kb in length with no evidence of a mutational hot spot discerned. The lack of correlation between the phenotype of 18 affected males from these 7 families and the location and size of the GPC3 gene mutations suggest that SGBS is caused by a nonfunctional GPC3 protein.
Hughes-Benzie
R M
RM
Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Canada.
Pilia
G
G
Xuan
J Y
JY
Hunter
A G
AG
Chen
E
E
Golabi
M
M
Hurst
J A
JA
Kobori
J
J
Marymee
K
K
Pagon
R A
RA
Punnett
H H
HH
Schelley
S
S
Tolmie
J L
JL
Wohlferd
M M
MM
Grossman
T
T
Schlessinger
D
D
MacKenzie
A E
AE
D000015:Abnormalities, Multiple / Q000235:genetics; D001345:Autoradiography; D015139:Blotting, Southern; D002872:Chromosome Deletion; D015342:DNA Probes; D005838:Genotype; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011509:Proteoglycans / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics
D015342:DNA Probes; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans