IS THE MITOCHONDRIAL-DNA INVOLVED IN DETERMINING SUSCEPTIBILITY TO MULTIPLE-SCLEROSIS

An increasing number of case reports on Leber's hereditary optic neuro pathy (LHON) associated mitochondrial (mt)DNA point mutations in patie nts with multiple sclerosis (MS) raised the possibility that mitochond rial determinants may contribute to genetic susceptibility to MS. Thes e observations prompted many laboratories including ours to perform co mprehensive sequencing or large scale screening of the mtDNA in MS pat ients. Here we review the available data arguing for or against a mito chondrial hypothesis for MS. We conclude that pathogenic mtDNA point m utations are not associated with typical forms of this disease. A very small subgroup of MS patients, usually with prominent optic neuritis (PON), may carry pathogenic LHON mutations. This partial overlap betwe en the two diseases may be related to the association of MS with a mtD NA haplotype (a set of mtDNA polymorphisms) within which pathogenic LH ON mutations preferentially occur.