Laboratory Alzheimer's Neuroimaging & Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Alzheimers Res Ther. 2020 Nov 17;12(1):152. doi: 10.1186/s13195-020-00720-4.
A consensus protocol for genetic counselling and testing of familial dementia, the Italian Dominantly Inherited Alzheimer's and Frontotemporal Network (IT-DIAfN) protocol, has been developed in Italy by a network of expert dementia centres. The aim of this study is to evaluate feasibility and acceptability of the genetic counselling and testing process, as undertaken according to the IT-DIAfN protocol in one of the IT-DIAfN dementia research centres.
The protocol was tested by a multidisciplinary team at the IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy, on affected individuals with suspected inherited forms of Alzheimer's disease (AD) or frontotemporal dementia (FTD), and to healthy at-risk relatives. The genetic counselling and testing process consisted of (i) pre-test consultation and psychological assessment (ii) genetic testing, (iii) genetic test result disclosure and (iv) follow-up consultation and psychological assessment.
Twenty affected individuals from 17 families fulfilled the family history criteria of the IT-DIAfN protocol for suspected inherited dementia (17 for AD, 2 for FTD, 1 for inclusion body myopathy with Paget disease of bone and frontotemporal dementia) and were included in the protocol. Nineteen out of 20 affected individuals received the genetic test result (one left after the pre-test consultation being not ready to cope with an unfavourable outcome). A pathogenic mutation was found in 6 affected individuals (1 in PSEN1, 2 in PSEN2, 1 in GRN, 1 in MAPT, 1 in VCP). Eleven healthy at-risk relatives asked to undergo predictive testing and were included in the protocol. Three completed the protocol, including follow-up; one did not ask for the genetic test result after genetic testing; and eight withdrew before the genetic testing, mainly due to an increased awareness about the possible consequences of an unfavourable test result. To date, no catastrophic reactions were reported at the follow-up.
Our case series shows that a structured genetic counselling and testing protocol for inherited dementia can be implemented in both affected individuals and at-risk relatives in a research setting. The procedure was shown to be safe in terms of occurrence of catastrophic events. A formal validation in larger cohorts is needed.
意大利一个由专家痴呆症中心组成的网络制定了一项针对家族性痴呆症的遗传咨询和检测的共识协议，即意大利显性遗传性阿尔茨海默病和额颞叶网络（IT-DIAfN）协议。本研究旨在评估按照 IT-DIAfN 协议在 IT-DIAfN 痴呆症研究中心之一进行遗传咨询和检测过程的可行性和可接受性。
该协议由意大利布雷西亚圣约翰福利布雷蒂中心 IRCCS 多学科团队进行测试，针对疑似遗传性阿尔茨海默病（AD）或额颞叶痴呆（FTD）的患者，以及健康的高危亲属。遗传咨询和检测过程包括：（i）预测试咨询和心理评估；（ii）基因检测；（iii）基因检测结果披露；（iv）随访咨询和心理评估。
17 个家族中有 20 名疑似遗传性痴呆患者符合 IT-DIAfN 协议的家族史标准（17 例 AD，2 例 FTD，1 例伴有骨和额颞叶痴呆的包涵体肌病伴佩吉特病），并纳入该协议。20 名受影响的个体中有 19 名接受了基因检测结果（1 名在预测试咨询后离开，因无法应对不利结果而未接受检测）。在 6 名受影响的个体中发现了致病性突变（1 名 PSEN1，2 名 PSEN2，1 名 GRN，1 名 MAPT，1 名 VCP）。11 名健康的高危亲属要求进行预测性检测，并被纳入该协议。其中 3 人完成了该协议，包括随访；1 人在基因检测后未要求基因检测结果；8 人在基因检测前退出，主要是因为对不利检测结果的可能后果有了更多的认识。迄今为止，在随访中没有报告灾难性反应。
我们的病例系列表明，针对遗传性痴呆的结构化遗传咨询和检测协议可以在研究环境中对受影响的个体和高危亲属实施。该程序在灾难性事件的发生方面被证明是安全的。需要在更大的队列中进行正式验证。
