Whole exome sequencing identifies novel variant underlying hereditary spastic paraplegia in consanguineous Pakistani families

Shumaila Zulfiqar, Muhammad Tariq, Z. Ali, Ambrin Fatima, Joakim Klar, Uzma Abdullah, A. Ali, Shafaq Ramzan, S. He, Jianguo Zhang, Ayaz Khan, Suleman Shah, Sheraz Khan, Ehtishamul Haq Makhdoom, Jens Schuster, Niklas Dahl, Shahid Mahmood Baig

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)19-23
Number of pages5
JournalJournal of Clinical Neuroscience
Volume67
DOIs
Publication statusPublished - Sept 2019
Externally publishedYes

Keywords

  • Ataxia
  • Peripheral neuropathy
  • SPG11
  • SPG56
  • Spastic paraplegia

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