Clinical Features and Genetic Spectrum of Patients With Clinically Suspected Hereditary Progressive Spastic Paraplegia

作者：Yuzhi Shi, An Wang, Bin Chen, Xingao Wang, Songtao Niu, Wei Li, Shaowu Li, Zaiqiang Zhang · 发表于：Frontiers in Neurology · 年份：2022 · DOI：10.3389/fneur.2022.872927 · 被引用次数：12 · 研究领域：Hereditary Neurological Disorders、Peripheral Neuropathies and Disorders、Amyotrophic Lateral Sclerosis Research

Background and Purpose A variety of hereditary diseases overlap with neurological phenotypes or even share genes with hereditary spastic paraplegia (HSP). The aim of this study was to determine the clinical features and genetic spectrum of patients with clinically suspected HSPs. Methods A total of 52 patients with clinically suspected HSPs were enrolled in this study. All the patients underwent next-generation sequencing (NGS) and triplet repeat primed PCR to screen for the dynamic mutations typical of spinocerebellar ataxia (SCA). Multiplex ligation-dependent probe amplification (MLPA) was further conducted in patients with no causative genetic mutations detected to examine for large deletions and duplications in genes of SPAST, ATL1, REEP1, PGN, and SPG11 . Clinical characteristics and findings of brain MRI were analyzed in patients with definite diagnoses. Results The mean age of the patients studied was 36.90 ± 14.57 years. 75% (39/52) of patients manifested a phenotype of complex form of HSPs. A genetic diagnosis was made in 51.9% (27/52) of patients, of whom 40.3% (21/52) of patients had mutations in HSPs genes ( SPG4/SPG6/SPG8/SPG11/SPG15/SPG78/SPG5A ) and 11.5% (6/52) of patients had mutations in SCAs genes ( SCA3/SCA17/SCA28 ). SPG4 and SPG11 were the most common cause of pure form of HSPs (5/6, 83.3%) and complex form of HSPs (5/15, 33.3%), respectively. Gait disturbance was the most common initial symptom in both the patients with HSPs (15/21) and in patients with...