Kadyshev V V, Zolnikova I V, Khalanskaya O V, Stepanova A A, Kutsev S I
N.P. Bochkov Research Centre for Medical Genetics, Moscow, Russia.
Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia.
Vestn Oftalmol. 2022;138(4):48-57. doi: 10.17116/oftalma202213804148.
To present the main aspects of interdisciplinary diagnostics of patients with hereditary retinal diseases and the first results of the follow-up of patients with inherited retinal dystrophies (IRD) caused by biallelic mutations in the gene after gene replacement therapy in Russia.
The cohort of patients consisted of six children (5-15 years old) with the diagnosis of Leber amaurosis type 2. All patients underwent a multi-disciplinary examination using conventional clinical, instrumental and molecular-genetic methods. Genetic diagnosis was established based on the results of two-stage DNA diagnostics using high-performance parallel sequencing of a custom panel and family segregation analysis by Sanger sequencing.
In the Research Centre for Medical Genetics the first group of Russian patients with an orphan inherited retinal disease was verified, they underwent subretinal injection of the gene replacement drug Voretigene neparvovec (12 eyes) in the Helmholtz National Medical Research Center of Eye Diseases. According to the regulated terms of monitoring gene therapy patients, they were examined in the Research Centre for Medical Genetics after 1, 3, 6 and 12 months, and then once per year. Thus, the available data allows us to analyze the first results 3 months after the treatment.
The presented data on inherited retinal dystrophies caused by biallelic mutations in the gene emphasize the need to change the diagnostic algorithm in the ophthalmic practice. The use of clinical instrumental and molecular genetic diagnostic methods makes it possible to apply etiotropic treatment to patients with a disabling disease that was previously considered untreatable. The gene replacement drug Voretigene neparvovec registered in Russia showed irrefutable first positive results in all targeted patients.
介绍遗传性视网膜疾病患者跨学科诊断的主要方面，以及俄罗斯基因替代治疗后由双等位基因突变引起的遗传性视网膜营养不良（IRD）患者随访的初步结果。
该患者队列由6名诊断为2型勒伯氏先天性黑蒙的儿童（5 - 15岁）组成。所有患者均采用传统临床、仪器和分子遗传学方法进行了多学科检查。基于使用定制面板的高性能平行测序和桑格测序进行的家系分离分析的两阶段DNA诊断结果建立了基因诊断。
在医学遗传学研究中心，首批俄罗斯孤儿遗传性视网膜疾病患者得到确诊，他们在国立赫尔姆霍茨眼疾病医学研究中心接受了视网膜下注射基因替代药物维替泊芬（12只眼）。根据基因治疗患者的规定监测期限，他们在1、3、6和12个月后在医学遗传学研究中心接受检查，然后每年检查一次。因此，现有数据使我们能够分析治疗后3个月的初步结果。
关于由双等位基因突变引起的遗传性视网膜营养不良的现有数据强调了眼科实践中改变诊断算法的必要性。临床仪器和分子遗传学诊断方法的使用使得对以前被认为无法治疗的致残性疾病患者应用病因治疗成为可能。在俄罗斯注册的基因替代药物维替泊芬在所有目标患者中都显示出无可争议的首个阳性结果。
