在两个患有痉挛性截瘫的巴基斯坦家庭中鉴定出罕见的新型CYP2U1和ZFYVE26变体。

Rare novel CYP2U1 and ZFYVE26 variants identified in two Pakistani families with spastic paraplegia.

作者信息

Bibi Farah, Efthymiou Stephanie, Bourinaris Thomas, Tariq Ambreen, Zafar Faisal, Rana Nouzhat, Salpietro Vincenzo, Houlden Henry, Raja Ghazala Kaukab, Saeed Sadia, Minhas Nasir Mahmood

机构信息

University Institute of Biochemistry & Biotechnology, PMAS - Arid Agriculture University, Rawalpindi 43600, Pakistan.

Department of Neuromuscular disorders, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.

出版信息

J Neurol Sci. 2020 Apr 15;411:116669. doi: 10.1016/j.jns.2020.116669. Epub 2020 Jan 11.

DOI:10.1016/j.jns.2020.116669

PMID:32006740

Abstract

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.

摘要