A novel 3-bp deletion in the PANK2 gene of Dutch patients with pantothenate kinase-associated neurodegeneration: evidence for a founder effect

Neurogenetics. 2005 Dec;6(4):201-7. doi: 10.1007/s10048-005-0018-9. Epub 2005 Oct 21.


Mutation analysis was performed in four apparently unrelated Dutch families with pantothenate kinase-associated neurodegeneration, formerly known as Hallervorden-Spatz syndrome. A novel 3-bp deletion encompassing the nucleotides GAG at positions 1,142 to 1,144 of exon 5 of the PANK2 gene was found in all patients. One patient was compound heterozygous; she also carried a novel nonsense mutation (Ser68Stop). The other patients were homozygous for the 1142_1144delGAG mutation. The 1142_1144delGAG mutation was also found in a German patient of unknown descent. We used polymorphic microsatellite markers flanking the PANK2 gene (spanning a region of approximately 8 cM) for haplotype analyses in all these families. A conserved haplotype of 1.5 cM was found for the 1142_1144delGAG mutation carriers. All the Dutch families originated from the same geographical region within the Netherlands. The results indicate a founder effect and suggest that the 1142_1144delGAG mutation probably originated from one common ancestor. It was estimated that this mutation arose at the beginning of the ninth century, approximately 38 generations ago.

MeSH terms

  • Base Sequence
  • Child
  • Child, Preschool
  • Female
  • Founder Effect
  • Gene Deletion*
  • Homozygote
  • Humans
  • Male
  • Microsatellite Repeats
  • Molecular Sequence Data
  • Netherlands
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / pathology*
  • Pantothenate Kinase-Associated Neurodegeneration / genetics*
  • Pedigree
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Polymorphism, Genetic


  • Phosphotransferases (Alcohol Group Acceptor)
  • pantothenate kinase