Rare novel CYP2U1 and ZFYVE26 variants identified in two Pakistani families with spastic paraplegia
Rare novel CYP2U1 and ZFYVE26 variants identified in two Pakistani families with spastic paraplegia
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DOI：
10.1016/j.jns.2020.116669
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发表时间：
2020-04-15
影响因子：
4.4
通讯作者：
Minhas, Nasir Mahmood
中科院分区：
文献类型：
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作者：
Bibi, Farah;Efthymiou, Stephanie;Minhas, Nasir Mahmood
背景：遗传性痉挛性截瘫（HSP）是一组临床和遗传上异质性的退行性疾病，其特征是下肢进行性痉挛和无力。本研究旨在鉴定两个不相关的近亲巴基斯坦家庭中存在两种不同形式的 HSP 的致病基因变异。方法：在两个家庭中进行全外显子组测序（WES），并通过桑格测序和分离分析验证变异。分析：在家庭 A 中，在一个家庭中鉴定出 ZFYVE26 纯合致病性变异。而在 B 家族中，在 4 名具有 SPG56 临床特征的受影响个体中发现了 CYP2U1 移码变异。我们的研究是巴基斯坦人群中导致 HSP 的 ZFYVE26 突变的第一份报告，也是巴基斯坦家庭中 CYP2U1 的第二份报告。结论：我们的研究结果增强了与两种罕见的常染色体隐性 HSP 基因相关的临床和遗传变异性，突出了 HSP 的复杂性。这些发现进一步强调了 WES 作为强大诊断工具的有用性。
Bakground: Hereditary Spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of degenerative disorders characterized by progressive spasticity and weakness of the lower limbs. This study aimed to identify causative gene variants in two unrelated consanguineous Pakistani families presented with 2 different forms of HSP.Methods: Whole exome sequencing (WES) was performed in the two families and variants were validated by Sanger sequencing and segregation analysis.Analysis: In family A, a homozygous pathogenic variant in ZFYVE26 was identified in one family. While in family B, a frameshift variant in CYP2U1 was identified in 4 affected individuals presented with clinical features of SPG56. Our study is the first report of ZFYVE26 mutations causing HSP in the Pakistani population and the second report of CYP2U1 in a Pakistani family.Conclusions: Our findings enhance the clinical and genetic variability associated with two rare autosomal recessive HSP genes, highlighting the complexity of HSPs. These findings further emphasize the usefulness of WES as a powerful diagnostic tool.