Abstract

Purpose

SPG76 is one of the rare forms of hereditary spastic paraplegia (HSP) which causes by mutations in the CAPN1 gene. The mode of inheritance of SPG76 is autosomal recessive (AR) and so far, only 24 families and 25 mutations in this gene have been reported worldwide. These mutations have been associated with a spectrum of disorders from pure HSP to spastic ataxia. HSP genetically is one of the most heterogeneous neurological disorders and to date, 79 types of HSP (SPG1-SPG79) have been identified, however, it has been suggested that many HSP-genes, particularly in AR-HSPs, remained unknown. AR-HSPs clinically overlap with other neurodegenerative disorders, making an accurate diagnosis of the disease difficult. Therefore, in addition to clinical examination, a high throughout genetic method like whole exome sequencing (WES) may be necessary for the diagnosis of this type of neurodegenerative disorders.

Methods and Results

Herein, we present the clinical features and results of WES in the first Iranian family with a novel CAPN1 variant, c.C853T:p.R285* and pure HSP.

Conclusion

Some of the previous studies have mentioned that the “spasticity-ataxia phenotype might be conducted to the diagnosis of SPG76” but recently the number of pure HSP patients with CAPN1 mutation is increasing. The present study also expands the mutation spectrum of pure CAPN1-related SPG76; emphasizing that CAPN1 screening is required in both pure HSP and spasticity-ataxia phenotypes. As noted in some other literature, we suggest the clinical spectrum of this disorder to be considered as “CAPN1-associated neurodegeneration”.

中文翻译：

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CAPN1 和遗传性痉挛性截瘫：伊朗家族中的一种新变异和基因型-表型相关性概述

摘要

目的

SPG76 是遗传性痉挛性截瘫 (HSP) 的一种罕见形式，由CAPN1突变引起基因。SPG76的遗传方式为常染色体隐性遗传（AR），迄今为止，全世界仅报道了该基因的24个家族和25个突变。这些突变与一系列疾病有关，从单纯的 HSP 到痉挛性共济失调。HSP 在遗传上是最具异质性的神经系统疾病之一，迄今为止，已鉴定出 79 种 HSP（SPG1-SPG79），然而，有人提出许多 HSP 基因，尤其是 AR-HSP 中的基因仍然未知。AR-HSP 在临床上与其他神经退行性疾病重叠，使得对该疾病的准确诊断变得困难。因此，除了临床检查外，诊断此类神经退行性疾病可能还需要采用全外显子组测序 (WES) 等高通量遗传方法。

方法和结果

在此，我们展示了具有新型CAPN1变体 c.C853T:p.R285* 和纯 HSP的第一个伊朗家族中 WES 的临床特征和结果。

结论

先前的一些研究提到“痉挛-共济失调表型可能用于诊断SPG76”，但最近CAPN1突变的纯HSP患者数量正在增加。本研究还扩展了纯CAPN1相关 SPG76的突变谱；强调在纯 HSP 和痉挛 - 共济失调表型中都需要CAPN1筛选。正如在其他一些文献中所指出的，我们建议将这种疾病的临床谱视为“ CAPN1相关神经变性”。