Novel likely disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis

J Neurol Sci. 2020 Jul 15:414:116826. doi: 10.1016/j.jns.2020.116826. Epub 2020 Apr 7.

Abstract

Background: Neuronal ceroid lipofuscinosis (NCL) is a hereditary lysosomal storage disease with progressive brain neurodegeneration. Mutations in ceroid lipofuscinosis neuronal protein 5 (CLN5) cause CLN5 disease, a severe condition characterized by seizures, visual failure, motor decline, and progressive cognitive deterioration. This study aimed to identify causative gene variants in Pakistani consanguineous families diagnosed with NCL.

Methods: After a thorough clinical and neuroradiological characterization, whole exome sequencing (WES) was performed in 3 patients from 2 unrelated families. Segregation analysis was subsequently performed through Sanger sequencing ANALYSIS: WES led to the identification of the 2 novel homozygous variants c.925_926del, (p.Leu309AlafsTer4) and c.477 T > C, (p.Cys159Arg).

Conclusion: In this study, we report two novel CLN5 cases in the Punjab region of Pakistan. Our observations will help clinicians observe and compare common and unique clinical features of NCL patients, further improving our current understanding of NCL.

Keywords: CLN5; Exome sequencing; Neuronal ceroid lipofuscinosis.

MeSH terms

  • Child
  • Exome Sequencing
  • Female
  • Homozygote
  • Humans
  • Lysosomal Membrane Proteins* / genetics
  • Male
  • Membrane Proteins / genetics
  • Neuronal Ceroid-Lipofuscinoses* / diagnostic imaging
  • Neuronal Ceroid-Lipofuscinoses* / genetics
  • Pakistan

Substances

  • CLN5 protein, human
  • Lysosomal Membrane Proteins
  • Membrane Proteins