Puomila Anu, Huoponen Kirsi, Mäntyjärvi Maija, Hämäläinen Petra, Paananen Reetta, Sankila Eeva-Marja, Savontaus Marja-Liisa, Somer Mirja, Nikoskelainen Eeva
Department of Medical Genetics, University of Turku, Turku, Finland.
Acta Ophthalmol Scand. 2005 Jun;83(3):337-46. doi: 10.1111/j.1600-0420.2005.00448.x.
To assess the clinical picture and molecular genetics of 14 Finnish families with dominant optic atrophy (DOA).
The clinical status of family members was based on the assessment of visual acuity, colour vision, visual fields and optic nerve appearance; 31 individuals were affected, two suspect and 21 unaffected. A total of 30 coding exons and exon- intron boundaries of the OPA1 gene were sequenced in order to detect mutations.
Half the patients were diagnosed at the age of < or = 20 years. Ten out of 20 affected individuals followed up for > or = 6 years had a progressive disease and 10 had a stable disease. According to WHO criteria, 36% of the affected patients were visually handicapped. Eight OPA1 pathogenic mutations, all but one novel, and 18 neutral polymorphisms were detected.
The most sensitive indicators of DOA were optic disc pallor and dyschromatopsia. With molecular genetic analysis, asymptomatic mutation carriers and DOA cases with a mild clinical outcome were ascertained. No mutational hotspot or Finnish major mutation in the OPA1 gene could be demonstrated as most families carried a unique mutation. No obvious genotype- phenotype correlation could be detected. Detailed clinical assessment and exclusion of non-DOA families prior to mutation screening are necessary for obtaining a high mutation detection rate.
评估14个芬兰显性遗传性视神经萎缩（DOA）家系的临床特征及分子遗传学情况。
通过评估家庭成员的视力、色觉、视野及视神经外观来确定临床状态；31人患病，2人疑似患病，21人未患病。对OPA1基因的30个编码外显子及外显子-内含子边界进行测序以检测突变。
半数患者在20岁及以下被诊断。20名接受随访≥6年的患病个体中，10人病情进展，10人病情稳定。根据世界卫生组织标准，36%的患病患者存在视力障碍。检测到8个OPA1致病突变，除1个外均为新突变，以及18个中性多态性。
DOA最敏感的指标是视盘苍白和色觉障碍。通过分子遗传学分析，确定了无症状突变携带者及临床症状较轻的DOA病例。由于大多数家系携带独特突变，未发现OPA1基因的突变热点或芬兰主要突变。未检测到明显的基因型-表型相关性。在进行突变筛查前，进行详细的临床评估并排除非DOA家系对于获得高突变检出率是必要的。
