Clinical and molecular genetic researches of a family with Leber's hereditary optic neuropathy

Objective To investigate the characterization of a four-generation large family with Leber's hereditary optic neuropathy (LHON). Methods The ophthalmological examinations of proband and other members of this family and controls were conducted, and Genomic DNA was isolated from whole blood of participants. Their DNA fragments were PCR-amplified using oligodeoxynucleotides corresponding to mtDNA at positions 3108-3717 for the G3460A mutation, 11,654-11,865 for the G11778A mutation, and 14,260-14,510 for the T14484C mutation, respectively. For the detection of the three primary mutations, testing of the gene sequence were performed on the amplified PCR segments. And molecular genetic analysis was performed on DNA extracted from the twins Ⅳ-3 and Ⅳ-4 to identify whether they are monozygotic twins(MZ) or dizygotic twins(DZ).Results The family history was consistent with a maternal inheritance and the proband exhibited a typical clinical feature of LHON. Molecular analysis identified the presence of the G11778A mutation. The twins Ⅳ-3, who was the proband, and Ⅳ-4 were dizygotic twins(DZ).Conclusion The family exhibited a typical LHON family clinically. It is the G11778A point mutation that leads to the presence of LHON in this large Chinese family. However, not all family members with the presence of the G11778A point mutation are inevitably suffered from LHON.