谁以及为何？肌萎缩侧索硬化症/额颞叶痴呆症与亨廷顿舞蹈症的症状前基因检测需求
Who and Why? Requests for Presymptomatic Genetic Testing for Amyotrophic Lateral Sclerosis/Frontotemporal Dementia vs Huntington Disease.
作者信息
Amador Maria Del Mar, Gargiulo Marcela, Boucher Christilla, Herson Ariane, Staraci Stéphanie, Salachas François, Clot Fabienne, Cazeneuve Cécile, Le Ber Isabelle, Durr Alexandra
机构信息
Maria del Mar Amador, Département de Neurologie (M.d.M.A., F.S.), Centre de Référence SLA de Paris, Assistance Publique-Hôpitaux de Paris, Sorbonne Université Hospital Pitié-Salpêtrière, Paris, France; Département de Génétique (M.d.M.A., M.G., C.B., A.H., S.S., A.D.), Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Sorbonne Université Hospital Pitié-Salpêtrière, Paris, France; Laboratory of Clinical Psychology (M.G.), Psychopathology and Psychoanalysis PCPP, EA 4056, University Paris Descartes, Sorbonne Paris City, Psychology Institute, Boulogne-Billancourt, France; Département de Génétique (F.C., C.C.), UF de Neurogénétique, Assistance Publique-Hôpitaux de Paris, Sorbonne Université Hospital Pitié-Salpêtrière; Centre de Référence des Démences Rares ou Précoces (I.L.B.), IM2A, Département de Neurologie, Assistance Publique-Hôpitaux de Paris, Sorbonne Université Hospital Pitié-Salpêtrière, Paris, France; and Sorbonne Université, Institut du Cerveau et de la Moelle épinière (ICM) (I.L.B., A.D.), Assistance Publique-Hôpitaux de Paris, INSERM, CNRS, Sorbonne Université Hospital Pitié-Salpêtrière, Paris, France.
出版信息
Neurol Genet. 2020 Dec 24;7(1):e538. doi: 10.1212/NXG.0000000000000538. eCollection 2021 Feb.
OBJECTIVE
We aimed to describe the population of subjects seeking presymptomatic counseling for amyotrophic lateral sclerosis and/or frontotemporal dementia (ALS/FTD) and compared them with those demanding the well-established presymptomatic test for Huntington disease (HD).
METHODS
We retrospectively examined the requests of a cohort of individuals at risk of familial ALS/FTD and 1 at risk of HD over the same time frame of 11 years. The individuals were seen in the referral center of our neurogenetics unit.
RESULTS
Of the 106 presymptomatic testing (PT) requests from subjects at risk of ALS/FTD, 65% were seen in the last 3 years. Over two-thirds of the subjects were at risk of carrying mutations responsible for ALS, FTD, or both. Sixty-two percent of the subjects came from families with a known hexanucleotide repeat expansion in . During the same period, we counseled 840 subjects at risk of HD. Subjects at risk of ALS/FTD had the presymptomatic test significantly sooner after being aware of their risk, but were older than those at risk of HD. The youngest subjects requesting the test had the highest disease load in the family ( < 0.05).
CONCLUSIONS
Demands for PT for ALS/FTD have been increasingly growing, particularly since the discovery of the gene. The major specificity of the genetic counseling for these diseases is the unpredictability of the clinical phenotype for most of the genes involved. Awareness of this added uncertainty does not prevent individuals from taking the test, as the dropout rate is not higher than that for HD.
目的
我们旨在描述寻求肌萎缩侧索硬化症和/或额颞叶痴呆（ALS/FTD）症状前咨询的人群，并将他们与那些要求进行成熟的亨廷顿病（HD）症状前检测的人群进行比较。
方法
我们回顾性研究了一组有家族性ALS/FTD风险的个体以及1名有HD风险的个体在11年同一时间范围内的咨询请求。这些个体在我们神经遗传学部门的转诊中心接受了检查。
结果
在106例有ALS/FTD风险的受试者的症状前检测（PT）请求中，65%是在过去3年提出的。超过三分之二的受试者有携带导致ALS、FTD或两者的突变的风险。62%的受试者来自已知 中有六核苷酸重复扩增的家庭。在同一时期，我们为840名有HD风险的受试者提供了咨询。有ALS/FTD风险的受试者在意识到自己的风险后显著更快地进行了症状前检测，但比有HD风险的受试者年龄更大。要求进行检测的最年轻受试者在家族中的疾病负荷最高（<0.05）。
结论
对ALS/FTD的PT需求一直在增加，特别是自 基因被发现以来。这些疾病的遗传咨询的主要特殊性在于，对于大多数相关基因而言，临床表型具有不可预测性。意识到这种额外的不确定性并没有阻止个体进行检测，因为退出率并不高于HD。
Zotero 插件