A novel mutation in ALS2 associated with severe and progressive infantile onset of spastic paralysis

J Neurogenet. 2017 Mar-Jun;31(1-2):26-29. doi: 10.1080/01677063.2017.1324441. Epub 2017 May 13.

Abstract

Infantile onset ascending spastic paralysis (IAHSP) is a type of recessively inherited spastic paraplegia. We investigated the clinical and genetic cause of a recessively inherited disorder in two siblings manifesting severe spasticity in the lower limbs which hindered their gait. A novel homozygous nonsense mutation c.1918 C > T (p.Arg640*) was identified after whole-exome sequencing within ALS2 in the DNA of both patients. The obligate carriers were heterozygous for the mutation and other unaffected members were homozygous for the wild type allele. The variant was absent from 100 control chromosomes and all public databases. This report extends the allelic heterogeneity of ALS2 mutations and emphasizes the importance of genetic testing for diagnosis of pediatric disorders.

Keywords: ALS2; Pakistan; Spastic paraplegia; alsin; infantile onset ascending spastic paralysis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Codon, Nonsense*
  • DNA Mutational Analysis
  • Female
  • Guanine Nucleotide Exchange Factors / genetics*
  • Homozygote
  • Humans
  • Male
  • Muscle Spasticity / genetics*
  • Pedigree
  • Spastic Paraplegia, Hereditary / genetics*
  • Spastic Paraplegia, Hereditary / pathology*

Substances

  • ALS2 protein, human
  • Codon, Nonsense
  • Guanine Nucleotide Exchange Factors

Supplementary concepts

  • Hereditary spastic paralysis, infantile onset ascending