Publication

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

Rump, P., Lemmink, HH., Verschuuren-Bemelmans, CC., Grootscholten, PM., Fock, JM., Hayflick, SJ., Westaway, SK., Vos, YJ. & van Essen, AJ., Dec-2005, In : Neurogenetics. 6, 4, p. 201-207 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

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
Pages (from-to)201-207
Number of pages7
JournalNeurogenetics
Volume6
Issue number4
Publication statusPublished - Dec-2005

    Keywords

  • Hallervorden-Spatz syndrome, PANK2, mutation, founder, haplotype, HALLERVORDEN-SPATZ-SYNDROME, IRON ACCUMULATION, COENZYME-A, MUTATIONS, NETHERLANDS, PHENOTYPE, DESCENT, HARP

ID: 4387002