Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China.
Department of Neurology, Jing'an District Center Hospital of Shanghai, 259 Xikang Road, Shanghai, 200040, China.
Orphanet J Rare Dis. 2019 Apr 25;14(1):83. doi: 10.1186/s13023-019-1053-1.
Hereditary spastic paraplegias (HSP) are of great clinical and genetic heterogeneity. According to the clinical features, HSP can be divided into pure or complicated subtypes which combined with other neurological symptoms including cerebellar ataxia. Up to date, 78 loci or genes have been implicated in HSP. CAPN1 was a novel gene detected recently for spastic paraplegia 76 (SPG76).
Patients referred to our clinic with spastic or spastic-ataxic gait were collected. Genetic testing of the probands were performed by target sequencing of a panel containing over 4000 known virulence genes. And the candidate mutations were further confirmed by polymerase chain reaction (PCR) and Sanger sequencing. The clinical materials of these patients were demonstrated retrospectively.
Two Chinese patients, both from consanguineous families, each carried a novel homozygous mutation of CAPN1, p.R48X and p.R339X. The male proband presented pure HSP subtype while the female proband presented complicated HSP symptoms with cerebellar ataxia. We then reviewed all the literatures of HSP patients carrying CAPN1 mutations and summarized the molecular spectrum and clinical characteristics of CAPN1-related SPG76.
These two SPG76 patients carrying CAPN1 mutations were the first reported in China. By reviewing the clinical manifestations of SPG76 patients, we validated the "spastic-ataxia" phenotype and emphasized the association between spasticity and ataxia, indicating the importance of CAPN1 screening in HSP patients.
遗传性痉挛性截瘫（HSP）具有很大的临床和遗传异质性。根据临床特征，HSP 可分为单纯或复杂亚型，伴有其他神经系统症状，包括小脑共济失调。迄今为止，已有 78 个位点或基因与 HSP 相关。CAPN1 是最近发现的与痉挛性截瘫 76 型（SPG76）相关的新基因。
收集我院以痉挛或痉挛性共济失调步态就诊的患者。对先证者进行目标测序，检测panel 中包含的 4000 多个已知致病基因。候选突变进一步通过聚合酶链反应（PCR）和 Sanger 测序进行验证。回顾性分析这些患者的临床资料。
两名中国患者均来自近亲家庭，各携带 CAPN1 基因的新型纯合突变，p.R48X 和 p.R339X。男性先证者表现为单纯 HSP 亚型，而女性先证者表现为伴有小脑共济失调的复杂 HSP 症状。我们随后回顾了所有携带 CAPN1 突变的 HSP 患者的文献，并总结了 CAPN1 相关 SPG76 的分子谱和临床特征。
这两名携带 CAPN1 突变的 SPG76 患者为中国首例报道。通过回顾 SPG76 患者的临床表现，我们验证了“痉挛-共济失调”表型，并强调了痉挛与共济失调之间的关联，提示在 HSP 患者中进行 CAPN1 筛查的重要性。
