Abstract

Introduction

Spastic paraplegia (SPG) is a syndrome characterised by lower limb spasticity, occurring alone or in association with other neurological manifestations. Despite of the new molecular technologies, many patients remain yet undiagnosed.

Objective

The purpose of this study was to describe the clinical presentation and molecular characteristics of a cohort of 27 patients from 18 different families with SPG in the south of Spain.

Methods

We used a targeted next-generation sequencing (NGS) approach to study a proband from each family.

Results

Variants in SPG11 gene were the most common cause of SPG in our area. We made a genetic diagnosis in 52% of cases, identified 3 novel variants and reclassified one uncertain variant in SPG11 gene as pathogenic variant. We identified a patient with two truncanting mutations in SPG11 gene and late onset disease and report another missense mutation outside of motor domain of KIF1A gene in a family with pure SPG.

Conclusion

Our study contributes to enhance the scientific knowledge of SPG. It is important to note the large group of cases (48%) that were not genetically diagnosed in our cohort. Therefore NGS approach is an efficient diagnostic tool, but it still large the number of non-diagnosed subjects, suggesting further genetic heterogeneity.

中文翻译：

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西班牙南部地区遗传性痉挛性截瘫的临床和分子特征

摘要

介绍

痉挛性截瘫 (SPG) 是一种以下肢痉挛为特征的综合征，单独发生或与其他神经系统表现有关。尽管有新的分子技术，许多患者仍未得到诊断。

客观的

本研究的目的是描述来自西班牙南部 18 个不同家族的 27 名 SPG 患者的临床表现和分子特征。

方法

我们使用靶向下一代测序 (NGS) 方法来研究每个家庭的先证者。

结果

SPG11基因变异是我们地区最常见的SPG原因。我们对 52% 的病例进行了基因诊断，鉴定了 3 个新变异，并将SPG11基因中的一个不确定变异重新分类为致病变异。我们确定了一名患者在SPG11基因中有两个截短突变和迟发性疾病，并在一个纯 SPG 家族中报告了另一个KIF1A基因运动域之外的错义突变。

结论

我们的研究有助于提高 SPG 的科学知识。重要的是要注意在我们的队列中未进行基因诊断的大量病例（48%）。因此 NGS 方法是一种有效的诊断工具，但它仍然有大量未确诊的受试者，这表明进一步的遗传异质性。