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

P. Rump, H. H. Lemmink, C. C. Verschuuren-Bemelmans, P. M. Grootscholten, J. M. Fock, Susan Hayflick, Shawn Westaway, Y. J. Vos, A. J. Van Essen

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13 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)201-207
Number of pages7
Issue number4
Publication statusPublished - Dec 2005



  • Founder
  • Hallervorden-Spatz syndrome
  • Haplotype
  • Mutation
  • PANK2

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

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