Clinical Genetics Unit, Department of Women's and Children's Health, University of Padova, 35128 Padova, Italy.
Kidney and Pancreas Transplant Surgery Unit, Regional Center for Diabetes Therapy, University of Padova, 35128 Padova, Italy.
Genes (Basel). 2024 Jul 18;15(7):937. doi: 10.3390/genes15070937.
Cystic fibrosis is a highly prevalent genetic disorder caused by biallelic pathogenic variants in the 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.
囊性纤维化是一种由 CFTR 基因双等位致病性变异引起的高度普遍遗传疾病，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。由于治疗和护理策略的改进，携带者筛查计划的日益普及，以及更精确和负担得起的分子诊断工具的发展，促使有风险的夫妇对产前诊断程序（包括胚胎植入前遗传学检测（PGT））的需求增加。然而，挑战依然存在：筛查计划的异质性、变异解释的细微差别以及新型治疗方法的出现，需要对遗传咨询采取周到和明智的方法。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，并被转诊到帕多瓦大学医院的遗传诊所进行遗传咨询，以确定是否有资格进行 PGT。共有 50 对夫妇被认为有资格进行该程序，因为有双等位致病性变异的风险。我们根据意大利医疗保健系统的情况报告并讨论了我们在这一系列病例中的经验，并概述了 CFTR 相关疾病的 PGT 遗传咨询中最相关的问题。
