Genetic heterogeneity in patients with pantothenate kinase-associated neurodegeneration and classic magnetic resonance imaging eye-of-the-tiger pattern

Mov Disord. 2006 Feb;21(2):252-4. doi: 10.1002/mds.20681.

Abstract

We performed a detailed molecular study in two unrelated families with pantothenate kinase-associated neurodegeneration (PKAN) and the specific magnetic resonance imaging (MRI) eye-of-the-tiger pattern. In the first family with classic PKAN, linkage analysis using polymorphic markers from the PANK2 region ruled out linkage with this locus, and no mutation of the PANK2 gene was found. In the second family with atypical PKAN, we identified a novel homozygous C-to-T transition at nucleotide 1069 of the PANK2 gene, which resulted in an arginine to tryptophane substitution at codon 357. As far as we are aware, this is the first case of classic PKAN with the specific MRI eye-of-the-tiger pattern not carrying a PANK2 mutation. Therefore, the present observation reinforces the notion of the phenotypic and genetic heterogeneity in PKAN.

MeSH terms

  • Adult
  • Amino Acid Substitution / genetics
  • Arginine / genetics
  • Brain / pathology*
  • Chromosome Mapping
  • Female
  • Genetic Heterogeneity*
  • Genetic Markers / genetics
  • Genotype
  • Globus Pallidus / pathology
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Neurologic Examination
  • Nucleotides / genetics
  • Pantothenate Kinase-Associated Neurodegeneration / diagnosis
  • Pantothenate Kinase-Associated Neurodegeneration / genetics*
  • Pedigree
  • Phenotype
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Tryptophan / genetics

Substances

  • Genetic Markers
  • Nucleotides
  • Tryptophan
  • Arginine
  • Phosphotransferases (Alcohol Group Acceptor)
  • pantothenate kinase