Istanbul University, Istanbul Medical Faculty, Department of Neurology, Istanbul, Turkey.
Bogazici University, Department of Molecular Biology and Genetics, Istanbul, Turkey.
Neurol Neurochir Pol. 2020;54(2):176-184. doi: 10.5603/PJNNS.a2020.0026. Epub 2020 Apr 3.
Hereditary spastic paraplegias (HSPs) are a heterogenous group of rare neurodegenerative disorders that present with lower limb spasticity. It is known as complicated HSP if spasticity is accompanied by additional features such as cognitive impairment, cerebellar syndrome, thin corpus callosum, or neuropathy. Most HSP families show autosomal dominant (AD) inheritance. On the other hand, autosomal recessive (AR) cases are also common because of the high frequency of consanguineous marriages in our country. This study aimed to investigate the clinical and genetic aetiology in a group of HSP patients.
We studied 21 patients from 17 families. Six of them presented with recessive inheritance. All index patients were screened for ATL1 and SPAST gene mutations to determine the prevalence of the most frequent types of HSP in our cohort. Whole exome sequencing was performed for an AD-HSP family, in combination with homozygosity mapping for five selected AR-HSP families.
Two novel causative variants were identified in PLP1 and SPG11 genes, respectively. Distribution of HSP mutations in our AD patients was found to be similar to European populations.
Our genetic studies confirmed that clinical analysis can be misleading when defining HSP subtypes. Genetic testing is an important tool for diagnosis and genetic counselling. However, in the majority of AR HSP cases, a genetic diagnosis is not possible.
遗传性痉挛性截瘫（HSP）是一组罕见的神经退行性疾病，表现为下肢痉挛。如果痉挛伴有认知障碍、小脑综合征、薄胼胝体或神经病等附加特征，则称为复杂 HSP。大多数 HSP 家族表现为常染色体显性（AD）遗传。另一方面，由于我国近亲结婚的高频率，常染色体隐性（AR）病例也很常见。本研究旨在调查一组 HSP 患者的临床和遗传病因。
我们研究了来自 17 个家庭的 21 名患者。其中 6 名呈隐性遗传。所有索引患者均进行 ATL1 和 SPAST 基因突变筛查，以确定我们队列中最常见的 HSP 类型的患病率。对一个 AD-HSP 家族进行全外显子组测序，并对 5 个选定的 AR-HSP 家族进行纯合子作图。
分别在 PLP1 和 SPG11 基因中发现了两个新的致病变异。我们发现 AD 患者的 HSP 突变分布与欧洲人群相似。
我们的遗传学研究证实，临床分析在定义 HSP 亚型时可能会产生误导。基因检测是诊断和遗传咨询的重要工具。然而，在大多数 AR-HSP 病例中，无法进行基因诊断。
