Identification of mitochondrial DNA ND1 T3866C mutation in three ethnic Han Chinese families affected with Leber's hereditary optic neuropathy / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To report on the clinical, genetic and molecular characteristics of three ethnic Han Chinese families affected with Leber's hereditary optic neuropathy (LHON).</p><p><b>METHODS</b>The three families were all diagnosed with LHON. Ophthalmologic examinations were conducted on the probands . The ND1, ND4 and ND6 genes of the mitochondrial DNA (mtDNA) were amplified with PCR respectively for the screening of three primary mutations G3460A, G11778A and T14484C. The entire mtDNA of the probands were also amplified by PCR.</p><p><b>RESULTS</b>Analysis of mtDNA in the three pedigrees has failed to find the presence of the three LHON associated mutations but presence of a homoplastic ND1 T3866C mutation in all probands and their matrilineal relatives . The probands had different levels of visual impairment. The penetrance in the three families has been calculated as 12.5%, 11.1% and 33.3%, respectively. The T3866C mutation has resulted in replacement of isoleucine at position 187 with theronine. The isoleucine at position 187 is located at one of the transmembrane domains of ND1 polypeptide.</p><p><b>CONCLUSION</b>Above results have suggested that the ND1 T3866C mutation might have been involved in the pathogenesis of LHON in the three Chinese families studied.</p>