Lack of Association between Leber’s Hereditary Optic Neuropathy Primary Point Mutations and Multiple Sclerosis in Iran

Abstract

The hypothesis that mitochondrial genes may implicate susceptibility to multiple sclerosis (MS) is supported by an increasing number of case reports on Leber’s hereditary optic neuropathy (LHON)-associated mitochondrial DNA (mtDNA) point mutations in patients with MS. A number of mtDNA mutations with primary pathogenic significance for LHON, a maternally inherited disease causing severe bilateral visual loss predominantly in young men, have been detected in patients with an MS-like phenotype. To evaluate the link between MS and LHON primary point mutations, we investigated 31 non-related Iranian clinically definite MS patients (23 females and 8 males) with optic nerve involvement, as well as 25 patients (16 females and 9 males) without involvement of the optic nerve as controls. Three patients had severe bilateral visual loss without any recovery. We searched for the presence of LHON mitochondrial mutations at nucleotide positions (np) 11,778, 3,460, and 14,484 by mutation-specific polymerase chain reaction and restriction fragment length polymorphism. Our results suggest that there is no association between Iranian patients with MS and mtDNA point mutations at np 11,778, 3,460, and 14,484.

Complex I deficiency in Persian multiple sclerosis patients

“…These mutations cause LHON, Leigh syndrome, Parkinson syndrome and various forms of encephalopathy [25 -27]. Although our previous study [28] for the presence of mtDNA mutations at nucleotides 11,778,14,484 and 3460 demonstrated that none of the MS patients exhibited any primary LHON mtDNA mutations, the available data for or against connection of MS to mitochondrial disorders indicate that there is the potential for such as association.…”

Population screening for association of mitochondrial haplogroups BM, J, K and M with multiple sclerosis: interrelation between haplogroup J and MS in Persian patients

“…2 A possible contribution of mtDNA to MS contingency has been postulated based on two observations: (1) predominant maternal transmission of the disease in concordant parent Á/child cases which may suggest mitochondrial inheritance or genomic imprinting; 4 and (2) association between inflammatory demyelination and Leber's hereditary optic neuropathy (LHON), a disease caused by maternally transmitted mtDNA point mutations. 5 Á 7 Although there is no evidence that either primary or secondary LHON mutations play a role in MS development, 8,9 mtDNA haplogroups J and X are shown to be risk factors in optic neuritis. 9,10 Optic neuritis is atrophy of the optic nerve, which frequently occurs in MS patients and shares several similarities with that of LHON.…”