PDF(Pubmed)
Abstract：
Cystic fibrosis is a highly prevalent genetic disorder caused by biallelic pathogenic variants in the CFTR gene, causing an altered function of the exocrine glands and a subsequent spectrum of hypofunctional and degenerative manifestations. The increasing availability of carrier screening programmes, the enhanced life expectancy of patients due to improved treatment and care strategies and the development of more precise and affordable molecular diagnostic tools have prompted a rise in demand of prenatal diagnosis procedures for at-risk couples, including Preimplantation Genetic Testing (PGT). However, challenges remain: heterogeneity among screening programmes, nuances of variant interpretation and availability of novel treatments demand a considerate and knowledgeable approach to genetic counselling. In this work, we retrospectively evaluated the molecular data of 92 unselected couples who received a diagnosis of CFTR-related status and were referred to the genetics clinic at the University Hospital of Padua for genetic counselling on eligibility for PGT. A total of 50 couples were considered eligible for the procedure based on risk of transmitting biallelic pathogenic variants. We report and discuss our experience with this case series in the context of the Italian medical care system and present an overview of the most relevant issues regarding genetic counselling for PGT in CFTR-related disorders.
摘要：
囊性纤维化是由CFTR基因的双等位基因致病变异引起的高度流行的遗传疾病,导致外分泌腺功能改变，随后出现一系列功能减退和退行性表现。越来越多的载体筛查方案，由于治疗和护理策略的改进以及更精确和负担得起的分子诊断工具的开发，患者的预期寿命得到了提高，这促使有风险夫妇对产前诊断程序的需求增加，包括植入前基因检测（PGT）。然而,挑战仍然存在：筛查方案之间的异质性，变异解释和新治疗方法的可用性的细微差别需要一种体贴和知识渊博的遗传咨询方法。在这项工作中,我们回顾性评估了92对未选择的夫妇的分子数据,这些夫妇接受了CFTR相关状态的诊断,并被转诊至帕多瓦大学医院的遗传学诊所接受关于PGT符合资格的遗传咨询.根据传播双等位基因致病变异的风险，总共有50对夫妇被认为符合该程序的条件。我们在意大利医疗保健系统的背景下报告并讨论了该病例系列的经验，并概述了有关CFTR相关疾病中PGT遗传咨询的最相关问题。
