Evidence for pathogenicity of variant ATM Val1729Leu in a family with ataxia telangiectasia

Neurogenetics. 2021 May;22(2):143-147. doi: 10.1007/s10048-021-00639-4. Epub 2021 Mar 29.

Abstract

Ataxia telangiectasia is a rare autosomal recessive multisystem disorder caused by mutations in the gene of ATM serine/threonine kinase. It is characterized by neurodegeneration, leading to severe ataxia, immunodeficiency, increased cancer susceptibility, and telangiectasia. Here, we discovered a co-segregation of two ATM gene variants with ataxia telangiectasia in an Egyptian family. While one of these variants (NM_000051.4(ATM_i001):p.(Val128*)) has previously been reported as pathogenic, the other one (NM_000051.4(ATM_i001):p.(Val1729Leu)) is regarded as a variant of uncertain significance. Our findings in this family provide additional evidence for causality of the second variant and argue that its status should be changed to pathogenic.

Keywords: ATM serine/threonine kinase; Ataxia telangiectasia; Egypt; Mutation; Pathogenicity.

Publication types

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

MeSH terms

  • Ataxia Telangiectasia / genetics*
  • Causality
  • Egypt
  • Exome Sequencing
  • Female
  • Genotype
  • Humans
  • Male
  • Mutation, Missense*
  • Pedigree
  • Phenotype
  • Point Mutation*
  • alpha-Fetoproteins / genetics

Substances

  • AFP protein, human
  • alpha-Fetoproteins