Brown J, Fingert J H, Taylor C M, Lake M, Sheffield V C, Stone E M
Department of Ophthalmology, University of Iowa College of Medicine, Iowa City, USA.
Arch Ophthalmol. 1997 Jan;115(1):95-9. doi: 10.1001/archopht.1997.01100150097016.
To refine the dominant optic atrophy locus, OPA1, on chromosome 3q and to characterize the phenotype of a 6-generation family pedigree affected with this disease.
Fifty-six family members had a complete eye examination. Clinical records of an additional 3 patients were reviewed. Goldmann perimetry and a 21-chip subtest of the Farnsworth-Munsell 100-Hue test were performed on selected patients. Affected patients, unaffected siblings, and potentially informative spouses were genotyped with short tandem repeat polymorphisms located on chromosome 3. The genotypic data were subjected to linkage analysis.
Thirty-four family members were found to be clinically affected. Most experienced vision loss (20/40 or poorer) in the first decade of life. Most (9 of the 16 eyes) progressed to 20/800 or poorer visual acuity by age 60 years, while 2 patients maintained visual acuities of 20/40 at that age. Affected patients had a 2- to 10-fold increase in the error score of a 21-chip subtest of the Farnsworth-Munsell 100-Hue test compared with age-matched unaffected family members. The optic nerve examination revealed temporal pallor and excavation in all affected individuals. Linkage analysis revealed significant lod scores with 9 markers. The highest lod score, 10.1 (theta = 0) [corrected], was obtained with marker D3S2305. Analysis of recombinants narrowed the disease interval to approximately 3.8 centimorgans, flanked by D3S3669 (centromeric) and D3S1305 (telomeric).
Most patients affected with dominant optic atrophy in this family progressed to legal blindness by middle age. Color vision testing is a sensitive method for detection of affected patients. The dominant optic atrophy locus, OPA1, has been refined by the identification of new flanking markers: D3S3669 (centromeric) and D3S1305 (telomeric).
对位于3号染色体q臂上的显性遗传性视神经萎缩基因座OPA1进行精细定位，并对一个患此病的6代家系的表型进行特征分析。
对56名家庭成员进行了全面的眼部检查。回顾了另外3例患者的临床记录。对部分患者进行了Goldmann视野检查以及Farnsworth-Munsell 100色调试验的21芯片子试验。对受累患者、未受累的同胞以及可能提供信息的配偶进行位于3号染色体上的短串联重复多态性基因分型。对基因分型数据进行连锁分析。
发现34名家庭成员有临床症状。大多数患者在生命的第一个十年出现视力丧失（20/40或更差）。到60岁时，大多数患者（16只眼中的9只）视力下降至20/800或更差，而2例患者在该年龄时视力维持在20/40。与年龄匹配的未受累家庭成员相比，受累患者在Farnsworth-Munsell 100色调试验的21芯片子试验中的误差评分增加了2至10倍。视神经检查显示所有受累个体均有颞侧苍白和凹陷。连锁分析显示与9个标记有显著的对数优势分数。标记D3S2305获得了最高的对数优势分数，为10.1（θ = 0）[校正后]。对重组体的分析将疾病区间缩小至约3.8厘摩，两侧分别为D3S3669（着丝粒侧）和D3S1305（端粒侧）。
该家系中大多数显性遗传性视神经萎缩患者到中年时发展为法定失明。色觉测试是检测受累患者的一种敏感方法。通过鉴定新的侧翼标记D3S3669（着丝粒侧）和D3S1305（端粒侧），对显性遗传性视神经萎缩基因座OPA1进行了精细定位。
