A small interstitial deletion in the GPC3 gene causes Simpson-Golabi-Behmel syndrome in a Dutch-Canadian family

• Published in: Journal of medical genetics Vol. 36; no. 1; pp. 57 - 58
• Main Authors: Xuan, Jian Y, Hughes-Benzie, Rhiannon M, MacKenzie, Alex E
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01-01-1999; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Biological and medical sciences; Bone and Bones - abnormalities; Canada; Chromosomes, Human, Pair 11 - genetics; Cloning; Complex syndromes; DNA polymerase; Female; Frameshift Mutation; glypican 3; Glypicans; Heparan Sulfate Proteoglycans; Heparitin Sulfate - blood; Heparitin Sulfate - genetics; Humans; Male; Males; Medical genetics; Medical sciences; Mutation; Pedigree; Proteoglycans - blood; Proteoglycans - genetics; Sequence Analysis, DNA; Sequence Deletion; Short Report; Simpson-Golabi-Behmel syndrome; Syndrome; Tumorigenesis; Wilms Tumor - complications; Wilms tumour; X Chromosome - genetics; Canada; Proteoglycan; Frameshift mutation; Cardiovascular disease; Dysmorphic facies; Genetic determinism; Kidney; Gene; Heart disease; Wilms tumor; Complex syndrome; Face; Kidney disease; Human; Dysplasia; Urinary system disease; Congenital; Stomatology; Family study; Growth excess; Cleft; Malignant tumor; Congenital disease; Simpson Golabi Behmel syndrome; Genetic disease; Case study; Lip; Phenotype; Malformation; Oral cavity disease; Palate
• ISSN: 0022-2593; 1468-6244
• DOI: 10.1136/jmg.36.1.57

Deletions in the heparan sulphate proteoglycan encoding glypican 3 (GPC3) gene have recently been documented in several Simpson-Golabi-Behmel syndrome (SGBS) families. However, no precisely defined SGBS mutation has been published. We report here a 13 base pair deletion which causes a frameshift and premature termination of the GPC3 gene in the Dutch-Canadian SGBS family in whom the trait was originally mapped. Our analysis shows that a discrete GPC3 disabling mutation is sufficient to cause SGBS. Furthermore, our finding of a GPC3 normal daughter of an SGBS carrier with skeletal abnormalities and Wilms tumour raises the possibility of a trans effect from the maternal carrier in SGBS kindreds.