A novel 3-bp deletion in the PANK2 gene of Dutch patients with pantothenate kinase-associated neurodegeneration: evidence for a founder effect |
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Authors: | P. Rump H. H. Lemmink C. C. Verschuuren-Bemelmans P. M. Grootscholten J. M. Fock S. J. Hayflick S. K. Westaway Y. J. Vos A. J. van Essen |
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Affiliation: | (1) Department of Clinical Genetics, University Medical Centre Groningen, University of Groningen, 30.001, 9700 RB Groningen, The Netherlands;(2) Department of Child Neurology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands;(3) Department of Molecular and Medical Genetics, School of Medicine, Oregon Health and Science University, Portland, OR, USA |
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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. |
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Keywords: | Hallervorden-Spatz syndrome PANK2 Mutation Founder Haplotype |
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