Berson E L
Berman-Gund Laboratory, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston.
Trans Am Ophthalmol Soc. 1990;88:355-88.
Ocular findings are presented in 17 unrelated patients with a form of autosomal dominant retinitis pigmentosa and the same C to A transversion in codon 23 of the rhodopsin gene. These patients (mean age, 36.6 years) had, on average, significantly better visual acuity and larger ERG amplitudes than 131 unrelated patients (mean age, 32.1 years) with autosomal dominant retinitis pigmentosa without this mutation. These 17 patients from separate families as well as 11 relatives with the mutation from 4 of these families showed interfamilial and intrafamilial variability with respect to severity of their ocular disease. This clinical heterogeneity among patients with the same mutation, with older patients sometimes showing less loss of visual function and less intraretinal bone spicule pigment than younger patients, suggests that some factor other than the gene defect itself is involved in the expression of this condition. This form of retinitis pigmentosa can now be detected by testing leukocyte DNA from peripheral blood. Patients so identified should have an ocular examination to determine the extent of their disease in view of the clinical heterogeneity that exists among patients with this mutation. Some mechanisms by which this mutation in the rhodopsin gene could lead to photoreceptor cell death are discussed. Opportunities for future clinical and laboratory research in search of possible treatments are considered.
本文报告了17例患有常染色体显性遗传性视网膜色素变性的无关患者的眼部检查结果，这些患者的视紫红质基因第23密码子均发生了相同的C到A的颠换。这些患者（平均年龄36.6岁）的平均视力和视网膜电图（ERG）振幅显著优于131例患有常染色体显性遗传性视网膜色素变性但无此突变的无关患者（平均年龄32.1岁）。来自不同家庭的这17名患者以及其中4个家庭的11名携带该突变的亲属，在眼部疾病严重程度方面表现出家族间和家族内的变异性。具有相同突变的患者存在临床异质性，老年患者有时比年轻患者视力功能丧失更少，视网膜内骨针状色素沉着也更少，这表明除了基因缺陷本身外，还有其他因素参与了这种疾病的表现。现在可以通过检测外周血白细胞DNA来检测这种形式的视网膜色素变性。鉴于携带该突变的患者存在临床异质性，确诊的患者应进行眼部检查以确定其疾病程度。文中还讨论了视紫红质基因中的这种突变可能导致光感受器细胞死亡的一些机制。同时也考虑了未来进行临床和实验室研究以寻找可能治疗方法的机会。
