Özdemir Taha Reşid, Gençpınar Pınar, Sarıteke Roza, Dagdas Safa M, Haspolat Senay, Tiftikcioglu Bedile I, Dündar Nihal Olgaç, Özyılmaz Berk
Genetic Diseases Evaluation Center, Izmir City Hospital, Izmir, Turkey.
Department of Medical Genetics, Health Sciences University, Izmir, Turkey.
Ann Indian Acad Neurol. 2025 May 1;28(3):353-362. doi: 10.4103/aian.aian_1068_24. Epub 2025 May 30.
Hereditary spastic paraplegia (HSP) is a group of neurodegenerative disorders characterized by genetic and clinical diversity. It often overlaps with other neurological conditions, such as cerebellar ataxia, which complicates diagnosis and highlights the importance of molecular genetic testing. This study aimed to investigate the molecular genetic basis of HSP in patients with clinical suspicion by identifying germline mutations in HSP-related genes and expanding the genetic spectrum of the disease through the discovery of novel variants.
Between 2019 and 2024, 74 patients from 71 families underwent genetic evaluation for germline mutations in 41 HSP-associated genes using a targeted next-generation sequencing panel, with Sanger sequencing performed on family members of patients with identified pathogenic variants to confirm segregation.
We identified 23 variants, including six novel likely pathogenic (LP) variants, one novel variant classified as variant of uncertain significance (VUS)-LP, seven known pathogenic variants, and nine VUS.
Overlapping clinical symptoms and laboratory findings between HSP and other neurological disorders frequently delay diagnosis, emphasizing the necessity of evaluating germline mutations in HSP genes for patients with suspected HSP to achieve a precise diagnosis. This study also contributes to the literature by reporting seven novel variants, enhancing the genetic understanding of HSP.
遗传性痉挛性截瘫（HSP）是一组以遗传和临床多样性为特征的神经退行性疾病。它常与其他神经系统疾病重叠，如小脑共济失调，这使得诊断变得复杂，并凸显了分子遗传学检测的重要性。本研究旨在通过鉴定HSP相关基因中的种系突变，并通过发现新的变异来扩展该疾病的遗传谱，从而调查临床疑似患者中HSP的分子遗传基础。
在2019年至2024年期间，来自71个家庭的74名患者使用靶向二代测序 panel对41个HSP相关基因中的种系突变进行了基因评估，对已鉴定出致病变异的患者家庭成员进行了桑格测序以确认分离情况。
我们鉴定出23个变异，包括6个新的可能致病（LP）变异、1个新的分类为意义未明变异（VUS）-LP的变异、7个已知致病变异和9个VUS。
HSP与其他神经系统疾病之间重叠的临床症状和实验室检查结果常常延误诊断，强调了对疑似HSP患者评估HSP基因种系突变以实现准确诊断的必要性。本研究还通过报告7个新变异为文献做出了贡献，增强了对HSP的遗传学理解。
