Genetic survey of primary LHON-causing mtDNA mutations as well as OPA1 and OPA3 mutations in 522 Chinese families with suspected hereditary optic neuropathy

Purpose: Autosomal dominant optic atrophy (ADOA) and Leber's hereditary optic neuropathy (LHON) are the commonest forms of hereditary optic atrophy The aim of this study was to report the results of molecular screening of the OPA1, OPA3 gene, and primary LHON-causing mtDNA mutations in a cohort of patients with suspected hereditary optic neuropathy. Methods: Patients and unaffected individuals from the 522 unrelated families were collected and underwent detailed ophthalmic examinations. Fourteen primary LHON-causing mtDNA mutations were initially screened by PCR-based sequencing methods for all patients except the individuals with a father-to-son transmission family history. All coding exons of the OPA1 and OPA3 gene were then screened for mutations by direct sequencing of PCR-amplified DNA fragments. A large deletion of the OPA1 gene was detected by multiplex ligation probe amplification (MLPA) assay. Results: 522 unrelated probands from 522 Chinese families were diagnosed with suspected hereditary neuropathy optic neuropathies. Molecular defects were identified in 322 probands (61.8% of the screened probands). Among these, 273 patients (84.9%) had an mtDNA mutation, 47 patients (14.6%) carried an OPA1 mutation, and 2 patients (0.6%) had an OPA3 mutation. Only 43% (118/273) patients of LHON had family history and the affected male-to-female ratio was 7.5:1 for the all probands. The three common primary LHON mutations were identified in 92.7 % (253/273) patients, rare primary mutations were detected in less 8% patients. Of the 47 probands with the OPA1 mutation, 42.5% cases had family history and the affected male-to-female ratio was 1.2:1 for the all probands. The mean onset age (19.25±8.42 years) of the LHON patients was significantly older than the one (8.21±7.52years) of the ADOA patients. There was a significant difference (P<0.01) in visual outcome between the patients with LHON and ADOA, with the mean logMAR visual acuity for patients with LHON mutations (1.3±0.65) being worse compared with those harboring OPA1 mutations (0.76±0.38). Forty mutations of the OPA1 gene were identified and 23 of which were novel. Three large OPA1 duplications were identified by the MLPA analysis. Conclusions: This study implies that the frequency of ADOA is much lower than that of LHON in Chinese compared with other ethnic groups. Purpose: To describe the results of the first 12 months of treatment with EPI-743(alphatocotrienol quinone) in a Brazilian cohort of Leber's Hereditary Optic Neuropathy (LHON), 11778 haplogroup J mutation. Methods: Six Brazilian patients with severe visual loss due to LHON were offered the experimental therapeutic EPI-743 …