Whole exome sequencing identifies novel variant underlying hereditary spastic paraplegia in consanguineous Pakistani families. (September 2019)

• Record Type: Journal Article
• Authors: Zulfiqar, Shumaila; Tariq, Muhammad; Ali, Zafar; Fatima, Ambrin; Klar, Joakim; Abdullah, Uzma; Ali, Aamir; Ramzan, Shafaq; He, Sijie; Zhang, Jianguo; Khan, Ayaz; Shah, Suleman; Khan, Sheraz; Makhdoom, Ehtishamul Haq; Schuster, Jens; Dahl, Niklas; Baig, Shahid Mahmood
• Is Part Of: Journal of clinical neuroscience. Volume 67(2019)
• Page Start: 19
• Page End: 23
• Publication Date: 2019-09
• Subjects: SPG11 -- SPG56 -- Ataxia -- Spastic paraplegia -- Peripheral neuropathy; Brain -- Surgery -- Periodicals; Neurosciences -- Periodicals; Nervous system -- Surgery -- Periodicals; Brain -- surgery -- Periodicals; Neurosurgical Procedures -- Periodicals; Neurosciences -- Periodicals; Electronic journals; 616.8
• DOI: 10.1016/j.jocn.2019.06.039
• Languages: English
• ISSNs: 0967-5868

Abstract

Highlights: Novel mutation: CYP2U1 gene. Known mutation: SPG11 gene. WES in HSPs. Abstract: Hereditary Spastic paraplegias (HSPs) are heterogeneous group of degenerative disorders characterized by progressive weakness and spasticity of the lower limbs, combined with additional neurological features. This study aimed to identify causative gene variants in two nonrelated consanguineous Pakistani families segregating HSP. Whole exome sequencing (WES) was performed on a total of five individuals from two families including four affected and one phenotypically normal individual. The variants were validated by Sanger sequencing and segregation analysis. In family A, a novel homozygous variant c.604G > A (p.Glu202Lys) was identified in the CYP2U1 gene with clinical symptoms of SPG56 in 3 siblings. Whereas, a previously reported variant c.5769delT (p.Ser1923Argfs*28) in the SPG11 gene was identified in family B manifesting clinical features of SPG11 in 3 affected individuals. Our combined findings add to the clinical and genetic variability associated with CYP2U1 and SPG11 variants highlighting the complexity of HSPs. These findings further emphasize the usefulness of WES as a powerful diagnostic tool.