Cruz-Mariño Tania, Vázquez-Mojena Yaimeé, Velázquez-Pérez Luis, González-Zaldívar Yanetza, Aguilera-Rodríguez Raúl, Velázquez-Santos Miguel, Estupiñán-Rodríguez Annelié, Laffita-Mesa José Miguel, Almaguer-Mederos Luis E, Paneque Milena
Predictive Genetics Department, Center for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba,
J Community Genet. 2015 Jul;6(3):265-73. doi: 10.1007/s12687-015-0226-4. Epub 2015 Apr 19.
Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by a CAG repeat expansion in the ATXN2 gene. Cuba has the highest prevalence (6.57 cases/10(5) inhabitants) of SCA2 in the world. The existence of 753 affected individuals and 7173 relatives at risk prompted the development in 2001 of the first predictive testing program in the country. The medical records of over 1193 individuals, who requested the test within a 13-year period, were analyzed retrospectively. The presymptomatic and the prenatal tests had uptake rates of 43.4 and 23.9 %, respectively. Several ethical challenges resulted from this program. These include the following: (1) withdrawal due to the initial protocol's length; (2) the request to participate by 16 at-risk adolescents; (3) the decision made by ten out of 33 couples with a test-positive fetus to carry the pregnancy to term, leading to de facto predictive testing of minors; (4) the elevated frequency of the ATXN2 gene large normal alleles (≥23 to 31 repeats) in the reference population. These issues have led to major changes in the guidelines of the predictive testing protocol: (1) the protocol length was shortened; (2) the inclusion criteria were expanded to reach at-risk adolescents with an interest in prenatal diagnosis; (3) interdisciplinary follow-up was offered to families in which test-positive fetuses were not aborted; (4) prenatal testing was made available to carriers of large normal alleles with ≥27 CAG repeats. The profiles of the participants were similar to those reported for other predictive testing programs for conditions like Huntington disease and familial adenomatous polyposis. The genetic counseling practices at the community level, the ample health education provided to the at-risk population, together with multidisciplinary and specialized attention to the affected families, are lessons from the Cuban experience that can be relevant for other international teams conducting predictive testing for other late-onset neurodegenerative disorders.
2型脊髓小脑共济失调（SCA2）是一种由ATXN2基因中CAG重复序列扩增引起的神经退行性疾病。古巴是世界上SCA2患病率最高的国家（每10万居民中有6.57例）。753名患者和7173名有患病风险的亲属的存在促使该国在2001年开展了首个预测性检测项目。对13年内申请检测的1193多人的病历进行了回顾性分析。症状前检测和产前检测的接受率分别为43.4%和23.9%。该项目引发了一些伦理挑战。这些挑战包括：（1）因初始方案过长而退出；（2）16名有患病风险的青少年要求参与；（3）33对胎儿检测呈阳性的夫妇中有10对决定将妊娠持续至足月，导致对未成年人进行了事实上的预测性检测；（4）参考人群中ATXN2基因大的正常等位基因（≥23至31个重复序列）频率升高。这些问题导致预测性检测方案的指导方针发生了重大变化：（1）缩短了方案长度；（2）扩大了纳入标准，以涵盖对产前诊断感兴趣的有患病风险的青少年；（3）为胎儿检测呈阳性但未流产的家庭提供跨学科随访；（4）为CAG重复序列≥27的大正常等位基因携带者提供产前检测。参与者的情况与其他针对亨廷顿病和家族性腺瘤性息肉病等疾病的预测性检测项目所报告的情况相似。社区层面的遗传咨询做法、为有患病风险人群提供的充分健康教育，以及对受影响家庭的多学科和专业化关注，都是古巴经验中的经验教训，可能对其他为其他迟发性神经退行性疾病进行预测性检测的国际团队具有借鉴意义。
