Koriath Carolin Anna Maria, Guntoro Fernando, Norsworthy Penelope, Dolzhenko Egor, Eberle Michael, Hensman Moss Davina J, Flower Michael, Hummerich Holger, Rosser Anne Elizabeth, Tabrizi Sarah J, Mead Simon, Wild Edward J
LMU University Hospital, Department of Psychiatry and Psychotherapie, Ludwig Maximilian University of Munich, Munchen, Bayern, Germany.
MRC Prion Unit at the UCL Institute of Prion Disease, London, UK.
J Neurol Neurosurg Psychiatry. 2025 Apr 10;96(5):466-469. doi: 10.1136/jnnp-2024-333602.
Genetic testing for Huntington's disease (HD) was initially usually positive but more recently the negative rate has increased: patients with negative HD tests are described as having HD phenocopy syndromes (HDPC). This study examines their clinical characteristics and investigates the genetic causes of HDPC.
Clinical data from neurogenetics clinics and HDPC gene-panel data were analysed. Additionally, a subset of 50 patients with HDPC underwent whole-genome sequencing (WGS) analysed via Expansion Hunter and Ingenuity Variant Analysis.
HDPC prevalence was estimated at 2.3-2.9 per 100 000. No clinical discriminators between patients with HD and HDPC could be identified. In the gene-panel data, deleterious variants and potentially deleterious variants were over-represented in cases versus controls. WGS analysis identified one expansion in a patient with HDPC.
The HDPC phenotype is consistent with HD, but the genotype is distinct. Both established deleterious variants and novel potentially deleterious variants in genes related to neurodegeneration contribute to HDPC.
亨廷顿舞蹈病（HD）的基因检测最初通常呈阳性，但最近阴性率有所上升：HD检测呈阴性的患者被描述为患有HD表型复制综合征（HDPC）。本研究考察了其临床特征，并探究了HDPC的遗传病因。
分析了神经遗传学诊所的临床数据以及HDPC基因检测板数据。此外，对50例HDPC患者的子集进行了全基因组测序（WGS），并通过扩展搜索器和英创思变异分析进行分析。
估计HDPC的患病率为每10万人中有2.3 - 2.9例。无法确定HD患者和HDPC患者之间的临床鉴别因素。在基因检测板数据中，有害变异和潜在有害变异在病例组中比对照组中更为常见。WGS分析在一名HDPC患者中发现了一个扩增。
HDPC的表型与HD一致，但基因型不同。与神经退行性变相关的基因中既有的有害变异和新的潜在有害变异都与HDPC有关。
