MOLECULAR GENETIC ANALYSIS OF JUVENILE MYOCLONIC EPILEPSY IN CONSANGUINEOUS SAUDI ARABIAN FAMILIES
Abstract number :
3.085
Submission category :
Year :
2002
Submission ID :
336
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Nichole Taske, Louise Bate, AbdulRahman Altahan, Tahir Obeid, Michele Rees, Mark Gardiner. Paediatrics and Child Health, University College London, London, United Kingdom; King Khalid University Hospital, Riyadh, Saudi Arabia; King Fahad National Guard Ho
RATIONALE: The aim is to map and identify the gene(s) responsible for autosomal recessive juvenile myoclonic epilepsy (JME) in consanguineous Saudi Arabian families.
METHODS: Three consanguineous Saudi Arabian families comprising a total of 13 individuals affected with JME have been ascertained. Inheritance of JME in all families is consistent with that of an autosomal recessive trait. To identify genomic regions harbouring potential susceptibility loci, a genome scan was conducted using polymorphic microsatellite markers spaced at approximate 10cM intervals. Homozygosity mapping, in which affected individuals of consanguineous families are predicted to have inherited identical chromosomal regions surrounding the disease locus from both parents, was then used to identify candidate regions.
RESULTS: Initial results from the genome scan identified a region on chromosome 6q27 that was homozygous by descent in 7 affected individuals of one large consanguineous family [[italic]Epilepsia[/italic] (2000), 41: 72]. Two point linkage analysis assuming autosomal recessive inheritance and a penetrance of 0.9 revealed a maximum LOD score of 4.39 ([theta]=0) at [italic]D6S281[/italic]. However, subsequent analysis of an additional affected individual of this family revealed that he was heterozygous at [italic]D6S281[/italic] which resulted in a maximum LOD score of 1.44 ([theta]=0) at [italic]D6S281[/italic]. Neither of the two remaining consanguineous Saudi Arabian families were consistent with linkage to this region.
CONCLUSIONS: Despite initial indications that a JME susceptibility locus resides on chromosome 6q in a single, large consanguineous Saudi Arabian family, typing of an additional affected individual of that family has revealed that under an autosomal recessive model, genes in this region are unlikely to be responsible for JME in this family. Alternative regions of homozygosity on chromosomes 7p12.3 and 9p22.1 are currently under investigation.
[Supported by: The Wellcome Trust
The Medical Research Council]