title: A novel 3-bp deletion in the PANK2 gene of Dutch patients with pantothenate kinase-associated neurodegeneration: evidence for a founder effect.
abstract: 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.
authors.affiliation: Department of Clinical Genetics, University Medical Centre Groningen, University of Groningen, 30.001, 9700 RB Groningen, The Netherlands. p.rump@medgen.umcg.nl
authors.forename: P
authors.initials: P
authors.lastname: Rump
authors.forename: H H
authors.initials: HH
authors.lastname: Lemmink
authors.forename: C C
authors.initials: CC
authors.lastname: Verschuuren-Bemelmans
authors.forename: P M
authors.initials: PM
authors.lastname: Grootscholten
authors.forename: J M
authors.initials: JM
authors.lastname: Fock
authors.forename: S J
authors.initials: SJ
authors.lastname: Hayflick
authors.forename: S K
authors.initials: SK
authors.lastname: Westaway
authors.forename: Y J
authors.initials: YJ
authors.lastname: Vos
authors.forename: A J
authors.initials: AJ
authors.lastname: van Essen
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D018703:Founder Effect; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009426:Netherlands; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology*; D006211:Pantothenate Kinase-Associated Neurodegeneration / Q000235:genetics*; D010375:Pedigree; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase