Confirmation of the G3635A mutation in the mitochondrial ND1 gene as a primary LHON mutation

童绎   朱益华   刘利娟   庄淑流   阳菊华

福建医科大学附属第一医院   福州东南眼科医院   福建医科大学医药生物工程中心   350004

Leber's hereditary optic neuropathy(LHON)is a maternally inherited disorder characteraized by a rapid bilateral loss of central vision and is due to mutations in mitochondrial DNA.Herein，we report the clinical and genetic characterization of two LHON families without the primary LHON-mutations in Chinese.Sequence analysis of the complete Mitochondrial DNA revealed the presence of homoplasmic ND1 G3635A mutation，and 31and 37 other variants，belonging to the East Asian haplogroup R11a and D4g in Family LHON-001 and LHON-019，respectively.The G3635A mutation changes a conversed serine residue to asparagine，which has been previously described in a single Russian LHON family and suggested to be contributing to LHON expression.Thus，the homoplasmic G3635A has been found in three independent LHON families belonging to different mtDNA haplogroups.In summary，our cases confirm that the pathogenicity of this mutation as a rare primary LHON mutation.