Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière, DMU Neuroscience 6, Paris, France.
Rouen University Hospital, Rouen, France.
Neurogenetics. 2021 Mar;22(1):71-79. doi: 10.1007/s10048-020-00633-2. Epub 2021 Jan 23.
Spastic ataxias are rare neurogenetic disorders involving spinocerebellar and pyramidal tracts. Many genes are involved. Among them, CAPN1, when mutated, is responsible for a complex inherited form of spastic paraplegia (SPG76). We report the largest published series of 21 novel patients with nine new CAPN1 disease-causing variants and their clinical characteristics from two European university hospitals (Paris and Stockholm). After a formal clinical examination, causative variants were identified by next-generation sequencing and confirmed by Sanger sequencing. CAPN1 variants are a rare cause (~ 1.4%) of young-adult-onset spastic ataxia; however, together with all published cases, they allowed us to better describe the clinical and genetic spectra of this form. Truncating variants are the most frequent, and missense variants lead to earlier age at onset in favor of an additional deleterious effect. Cerebellar ataxia with cerebellar atrophy, dysarthria and lower limb weakness are often associated with spasticity. We also suggest that cognitive impairment and depression should be assessed specifically in the follow-up of SPG76 cases.
痉挛性共济失调是一种罕见的神经遗传性疾病，涉及脊髓小脑和锥体束。许多基因参与其中。其中，CAPN1 基因突变可导致一种复杂的遗传性痉挛性截瘫（SPG76）。我们报告了来自两家欧洲大学医院（巴黎和斯德哥尔摩）的 21 名新患者和 9 种新 CAPN1 致病变异体的最大系列研究，这些患者以前都未发表过。经过正式的临床检查，通过下一代测序确定了致病变异体，并通过 Sanger 测序进行了确认。CAPN1 变异是年轻成人痉挛性共济失调的罕见病因（约 1.4%）；然而，结合所有已发表的病例，它们使我们能够更好地描述这种形式的临床和遗传谱。截断变异是最常见的，错义变异导致发病年龄更早，表明存在额外的有害影响。伴有小脑萎缩、构音障碍和下肢无力的小脑性共济失调常伴有痉挛。我们还建议在 SPG76 病例的随访中专门评估认知障碍和抑郁。
