Genetic linkage analysis of two Simpson-Golabi-Behmel syndrome families in our lab has been conducted. The closest linkage to SGBS was observed for the chromosome Xq26 locus HPRT. SGBS-Xq marker recombinations map the disease locus to the Xqcen-DXS425-SGBS-DXS1123-Xqter interval on Xq25-q27. The close linkage between the disease locus and the HPRT locus strongly suggests that the causative gene for SGBS is located in the chromosome Xq26 region and is disrupted by the translocation. SGBS shows significant clinical overlap with another overgrowth disorder called Beckwith-Wiedemann syndrome (BWS). Both disorders demonstrate an increased risk for developing embryonal tumours. Two genes from the BWS linked chromosome 11p15 region, IGF2 and H19, are known to normally undergo parental imprinting. Relaxation of this imprinting has recently been demonstrated in some BWS cases as well as in some instances of isolated Wilms' tumour (WT). Since SGBS and BWS have been postulated to result from distinct defects in a common pathway, we have studied the methylation pattern and transcriptional activity of IGF2 and H19 in isolated SGBS +/$-$WT tissue. No consistent methylation abnormalities were observed in genomic DNA isolated from SGBS leucocytes, placenta, skin fibroblasts or cleft lip tissues. Genotyping of H19 cDNA polymorphisms showed biallelic expression in both SGBS and normal placentas and monoallelic expression in one SGBS fibroblast. However monoallelic expression of IGF2 was seen in control placenta and fibroblast but biallelic expression of IGF2 was shown in one SGBS placenta, and two SGBS fibroblasts tissues. It would thus appear that loss of genomic imprinting may play a role in the pathogenesis of SGBS. This is the first example that we are aware of a trans imprinting function for a human gene. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/10070 |
| Date | January 1995 |
| Creators | Xuan, Jian Ying. |
| Contributors | Mackenzie, Alex, |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Detected Language | English |
| Type | Thesis |
| Format | 130 p. |
Page generated in 0.0014 seconds