title: A shared haplotype for dentatorubropallidoluysian atrophy (DRPLA) in Italian families testifies of the recent introduction of the mutation.
abstract: To clarify the population history of dentatorubropallidoluysian atrophy (DRPLA) in Italy and to date back the introduction of the mutation, we reconstructed extended haplotypes flanking the CAG repeat in 10 patients of Italian ancestry, analyzing their similarity/dissimilarity as a function of distance from the CAG repeat. Our aim was to compare the hypothesis of a single, recent genealogy connecting all the observed haplotypes with the alternative hypothesis of multiple introductions by more distantly related haplotypes from outer sources. Polymorphic DNA markers were chosen to cover a region of 153 kb flanking the CAG repeat, that is, informative for dating the age of the DNA segment unaffected by recombination. In all patients, an expansion of the ATN1 CAG segment was confirmed residing onto the same narrow haplotype described to be associated with the CAG expansion in the Japanese and Portuguese populations. We also observed the disruption of the DRPLA haplotype at longer distances, on both sides of the CAG. Our results are compatible with a single founder in the last 600 years, most likely before the last 270 years. These estimates for the Sicilian population largely overlap a period in which the Japanese haplotype with the DRPLA mutation could have been introduced by the Portuguese maritime travelers.
authors.affiliation: Institute of Translational Pharmacology, National Research Council of Italy, Rome, Italy.
authors.forename: Liana
authors.initials: L
authors.lastname: Veneziano
authors.affiliation: Institute of Translational Pharmacology, National Research Council of Italy, Rome, Italy.
authors.forename: Elide
authors.initials: E
authors.lastname: Mantuano
authors.affiliation: Department of Biopathology and Diagnostic Imaging, Tor Vergata University, Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Catalli
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Milan, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Gellera
authors.affiliation: Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (INSERM/UPMC Univ. Paris 6, UMR_S975; CNRS 7225), Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.affiliation: Neurology and Centre for Experimental Neurological Therapies (CENTERS), S. Andrea Hospital Site, La Sapienza University of Rome, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Romano
authors.affiliation: Institute of Translational Pharmacology, National Research Council of Italy, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Spadaro
authors.affiliation: Institute of Translational Pharmacology, National Research Council of Italy, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Frontali
authors.affiliation: Department of Biology, Tor Vergata University, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Novelletto
mesh_terms: D001284:Atrophy; D020029:Base Pairing / Q000235:genetics; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology*; D010375:Pedigree; D011995:Recombination, Genetic / Q000235:genetics