THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES QUEBEC COOPERATIVE STUDY OF FRIEDREICH'S ATAXIA Origin of Friedreich's Disease in Quebec

We have been able to trace 40 cases of classical Friedreich's disease from 14 previously unrelated French Canadian kindreds to one common ancestral couple arriving in New France in 1634: Jean Guyon and Mathurine Robin. One member of this couple presumably introduced one gene for Friedreich's disease into the French Canadian population. This gene has now been traced over 12 generations to both parents of the present cases. We plan to use this knowledge to study the spectrum of clinical manifestations of this gene and to carry out gene chromosomal localization studies, using the techniques of linkage and of molecular biology. Such studies in rare autosomal recessive disorders have previously been judged to be almost impossible. RESUME: Nous avons reussi a retracer le couple ancestral commun a 40 cas de Friedreich classique provenant de 14 families canadiennes-francaises prealablement non reliees. Ces ancetres communs (Jean Guyon et Mathurine Robin) sont arrives en Nouvelle-France en 1634. Un des deux membres du couple a presumement introduit un gene de Friedreich dans la population du Quebec. Ce gene a maintenant £te suivi sur 12 generations jusqu'aux deux parents de chacun des 40 cas presentement sous etude. Nous avons l'intention d'utiliser ces nouvelles connaissances pour etudier I'eventail des manifestations cliniques de ce gene et pour tenter de localiser le site chromosomique du gene a 1 'aide des techniques de linkage et de biologie moleculaire. De telles etudes etaient jusqu'ici consid£rees comme pratiquement impossibles pour des maladies autosomales recessives rares. Can. J. Neurol. Sci. 1984; 11:506-509 The Province of Quebec is ideal for genealogical studies of diseases because most of its inhabitants (5 of the 6 millions) are of French extraction, originating from a pool of 70,000 immigrants who crossed the Atlantic before 1760. Most of these immigrants are known and their descendants can be traced through all but complete church and/or civil records. Lately these records have been microfilmed and are in the process of being computarized for even easier access. Meanwhile documents such as "Le Dictionnaire G6n6alogique des Families Canadiennes" (C. Tanguay, Editions Elys6e); "Le Dictionnaire National des Canadiens Fran§ais, 1608-1760" (Institut Genealogique Drouin) and "Le Dictionnaire G6nealogique des Families du Quebec" (R. Jette\ Presses de l'Universite de Montreal, 1983) are available to researchers, in addition to hundreds of "R6pertoire de Paroisses" for most of the Catholic Faith parishes. These resources have been used previously in tracing the origin of various neurological diseases in Quebec, such as oculo-pharyngeal muscular dystrophy (Barbeau, 1966), familial agenesis of the corpus callosum with polyneuropathy (Andermann et al., 1972) and Huntington's chorea (Barbeau et al., 1964). A preliminary report from our group (Barbeau et al., 1976) attempted to trace the origin of Friedreich's disease in French Canadians from the study of four kindreds (13 cases). The search led to a total of 10 possible "founding couples" having lived in Nouvelle France in the 17th Century. In the present paper we would like to publish further data which now permits the identification of one of these common ancestral couples as having presumably introduced the Friedreich gene into the French Canadian population. SUBJECTS AND METHODS Genealogical studies were initiated for 14 different French Canadian kindreds, including 40 cases of a recessive ataxia conforming to all the classical criteria for Friedreich's disease as defined by Geoffroy et al. (1976). These patients were seen in one or more of the five Ataxia Clinics maintained in the Province of Quebec by "L' Association Canadienne de l'Ataxie de Friedreich", and were followed regularly by the authors. This is an ongoing study, and many more kindreds are still available, but genealogical data has not yet been gathered for them. No particular form of selection was used for the kindreds included in this study, except willingness to cooperate and proximity to the clinics. For each of the ataxia families, a control kindred From the Clinical Research Institute of Montreal (1), the University of Alger, Algeria (2), the Centre Hospitalier Universitaire de Sherbrooke (3), the Hopital de I'Enfant-Jgsus, Quebec (4), and the Hopital Sainte-Justine, Montreal (5). Reprint requests for the complete supplement (Phase 3, Part 3) to: Prof. Andr£ Barbeau, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7. 506 https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0317167100034971 Downloaded from https:/www.cambridge.org/core. IP address: 54.191.40.80, on 09 Apr 2017 at 10:00:34, subject to the Cambridge Core terms of use, available at LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES was also evaluated. These were selected at random from a pool of ongoing genealogical studies for other disorders in Quebec (Huntington's chorea, oculo-pharyngeal muscular dystrophy; dystonia musculorum deformans; myotonic dystrophy). None of the control kindreds were related to the ataxic kindreds, or contained known cases of spino-cerebellaror cerebellar disorders. Genetic/genealogical studies in a recessive disorder are more difficult than in a dominant disease, for it is necessary to prove that both the father and the mother descend from the same common ancestral couple, since each is an obligatory heterozygote. A similar requirement was mandatory for the control kindreds. A complete family tree, in French Canada, goes back 10 to 13 generations to the days of the French Regime (1608-1760). The maximum number of ancestral couples for each kindred (13 generations), assuming no consanguinous marriages between the descendants, would be 2,048. In fact the figure was always much lower, because the fertility rate of French Canadians in early colonial days was one of the highest in recorded history (Laberge, 1966) and the consanguinity rate always fairly high in isolated hamlets. For each kindred, ataxic and control independently, each branch in the ascending tree was followed all the way to the original French immigrant and recorded on especially prepared charts. Once the trees were completed, an index card was made for each couple identified. Cards from all kindreds were compared for common names.