LE JOURNAL CANAD1EN DES SCIENCES NEUROLOG1QUES
Quebec Cooperative Study of Friedreich's Ataxia.
Friedreich's Ataxia: Preliminary Results of some Genealogical Research
A. BARBEAU, M. LE SIEGE, G. BRETON, R. COALL1ER AND J. P. BOUCHARD
SUMMARY: A preliminary genealogical INTRODUCTION studied in two phases, first by Drs. investigation of all the known ancestors As demonstrated in the previous Raymond Robillard and Jean-Marc from the year 1608 of 4 apparently unre paper, all cases of ataxia studied in St-Hilaire of Montreal (1960-1965) lated French Canadian kindreds with this cooperative study are considered and later by Barbeau (1970-1975). Friedreich's ataxia reveals that the origi autosomal recessive. This is in con This kindred with a dominant form of nal ataxia gene in the province of Quebec spinocerebellar ataxia originated, as was present within a core of no more than tradiction to the findings of Bell and 10 families living in Quebec City in the Carmichael (1939) who found a do far as we could trace from interviews mid-1600's. minant form, albeit in rare instances. and personal examinations, from a In a study of a large American Mont-Louis family in the Gaspe RESUME: Une etude genealogique kindred, Schut (1950, 1951) had also Peninsula in the late 18th century. It preliminaire de tous les ancetres connus shown that a family with dominantly was also known that branches of this jusqu'en 1608 de qitatre families inherited spinocerebellar degenera kindred had lived in Acadia (New Canadiennes-Francaises apparemment tion included some instances of typi Brunswick) and some descendants non reliees mais souffrant d'ataxie de cal Friedreich's ataxia. Because a had emigrated to Louisiana. We are Friedreich, a montre que le gene original dominant form of spinocerebellar de reliably informed that ataxia is a d'ataxie dans la province de Quebec etait generation is frequent in the Province common occurrence among Cajuns present parmi un noyau maximum de 10 of Quebec (see subjects and of that state. families vivant dans la ville de Quebec vers le milieu dit 17e siecle. methods), one question raised early In the course of the genetic in our study was the possible link analysis we enquired as to the names, between that large kindred and our places of birth and death of the ances cases of Friedreich's ataxia. Another tors as far back as could be remem problem was whether there is a single bered by the oldest members of each disease in all our typical cases (Group family. The Public Archives in I) or whether the same phenotype Quebec, Trois-Rivieres, Montreal can mask a number of heterogeneous and a number of smaller entities. Studying the genealogical municipalities supplied records to background of our kindreds helps 1750. In this search we were helped solve these questions. The Province by cooperation of active members of of Quebec is ideal for such a task "La Societe de Genealogie because most of its inhabitants of Canadienne-Francaise", and by stu French extraction are descendants dents employed by the "Association from an original stock of 60-70,000 Canadienne de l'Ataxie de Fried immigrants to New France before reich" on a Local Initiative Project. 1760; because of its very high con Subsequent investigation into earlier sanguinity rate in the first genera generations was done with the help of tions, and finally because church re two invaluable documents: "Le Dic- cords are mostly intact and available. tionnaire Genealogique des Families Therefore, a genealogical search for Canadiennes", C. Tanguay, Editions any common ancestors was included Elysee; and "Le Dictionnaire Na in the protocol of the cooperative tional des Canadiens-Francais study. The present report is incom 1608-1760", the latter published by plete and fragmentary but it should ITnstitut Genealogique Drouin in a help clear the way for further studies. limited edition. From the Clinical Research Institute of Montreal, Because this research had a low and I'Hopital de I'Enfant-Jesus, Quebec City. priority and was done in large part as Reprint requests for the complete supplement on SUBJECTS AND METHODS a hobby, we completed the investiga Friedreich's ataxia to: Dr. Andre Barbeau, Clinical Research Institute of Montreal, 110 Pine Avenue The comparison kindred which tion of only 4 of the 12 kindreds West, Montreal, H2W 1R7 Quebec, Canada. we attempted to link had been studied at the Hotel-Dieu Hospital,
Vol. 3, No. 4 NOVEMBER 1976-303
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TABLE 1 Common Ancestors to 4 Kindreds of Ataxia Names of Early Common Ancestors Site of Marriage Local Habitation Site of Origin in France Jean Aymard Quebec Poitou Marie Bineau — La Rochelle Gervais Bisson Quebec Maine Marie Lereau Jean de Noyon Dearfield (N.-A.) St-Pierre de Rouen Trois-Rivieres (Normandie) Marie Chauvin Boucherville Normandie Mathieu Choret N-D. de Cogne Quebec La Rochelle (Aunis) (La Rochelle) Beauport Sebastienne Veillon Ste-Famille (He d'Orleans) Saintes (Angoumois) Pierre Loignon Francoise Roussin Quebec Ste-Famille (He d'Orleans) Perche Robert Drouin Marie Dubois Quebec Perche Charles Sevestre Marie Pichon Quebec Paris (Ue-de-France) Jean Guyon Mathurine Robin Quebec Perche Noel Morin Ile-de-France Helene Desportes Quebec Quebec Lisieux (Normandie) Leonard Leblanc Marie Riton Quebec Quebec Marche
but other families are being studied. RESULTS AND DISCUSSION are so many possible ways for a given A complete family tree, in French Many difficulties (such as incom patient to be traced back to the com Canada, goes back 10 to 13 genera plete records, occasional illegitimate mon ancestor that it is almost impos tions to the early days of the colony births, errors in transcription or spell sible to know the actual transmitters (1608-1700). In general, for the 4 fam ing from the original documents) and of the abnormal gene. ilies studied, we were able to trace lack of time precluded complete an We have, of the thousands of pos 12 generations (an average of 2,048 cestral trees on all the kindreds in sible ancestral couples, identified 10 names of "primary" possible prog cluded in our cooperative survey. marriages that appear in all 4 kin enitors per family). Many names ap Thus the present summary is only a dreds investigated (Table 1). For pear a number of times, because of progress report of an investigation each of these common "primary" consanguinity in the later genera which will take many years to con ancestors, trees such as the one illus tions. clude. To date we have traced all the trated in Figure 1 could be drawn, Once the 4 trees were completed Canadian ancestors of four kindred further complicating the situation on special large sheets, an index-card (herewith labelled kindreds A to D). (when we had completed 3 kindreds, was made for each name recorded in A total of 8,260 names of ancestors there were 22 common ancestral all known generations in Canada, for were obtained on index cards show couples). It is hoped that the addition each family. In this way, names of ing a large number of links, and of further complete kindreds will ancestors appearing in more than one consanguinous marriages. This is il permit us to identify the one common family could be determined, to help lustrated in Figures 1, 2 and 3. ancestral couple who may even have pin-point consanguinous marriages. For example, in Figure 1 there are lived in France before 1608 (date of Names appearing in all 4 families at least 14 consanguinous marriages. establishment of Quebec City). At were prepared to list all their possible Each time this occurs the risk of the present time we are unable to do descendants. Links between the 4 transmission of a given gene is multi so, but some common characteristics original families were thus de plied. In this geographically and ling of the "primary" ancestral couples lineated. uistically isolated population there permit us to be fairly confident that
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EC. C. there is one common genetic source to at least 4 of our typical Friedreich's ataxia kindreds. All couples and their first generation de scendants, although originating from diversified regions of France, lived in Quebec City between 1615 and 1680, when the immigrant population of "La Nouvelle France" numbered 3,802. It is thus highly likely that they all knew each other quite well. This is further attested to by the fact that within the 3 subsequent generations it was possible to show marriages between descendents that linked at least 9 of the 10 "primary" ancestral couples. In conslusion, we can state with some degree of certainty that the original "Friedreich's ataxia gene" in Quebec, at least for the kindreds included in our cooperative survey, • . . 6 66ih must have been present within a core KINDRED-A KINDRED-B KINDRED-B of 10 families living in Quebec City in the mid-1600's (Table 1 for list). For Figure I — An example of many consanguinous marriages in a French Canadian family each of these 10 "primary" couples it with typical Friedreich's ataxia, and of the links between kindreds A and B. Open can be shown that the gene could square = normal male, solid square = ataxic male, open circle = normal female, have descended directly to the pa solid circle = ataxic female. tients included in our survey (Figure 4). Further investigation is necessary to correctly identify the actual com mon ancestor to all our typical cases J:F B. D—r—O MrA.C of Friedreich's ataxia, and to show whether there is a link with the do minant form of spinocerebellar de generations also identified in R:A. V. CD—r—O F. Q Quebec. All that can be stated now is that the family surname of the earliest J identified case of the dominant form does exist amongst the descendents of some of the "primary" couples. If a link can be discovered, this would complicate genetic analysis of the phenotypic expressions of the atax ias. Until all our kindreds have been studied, it will be impossible to use the genealogical argument to decide whether we are dealing with one or many disease entities. Nevertheless, -a we feel that if this research approach is eventually successful, it will be one na'iD^l of the most powerful instruments for the understanding and nosological KINDRED-C £¥Vh classification of the ataxias. KINDRED-B Figure 2 — Possible links between kindreds B and C with Friedreich's ataxia in French Canada. Open square = normal male, solid square = ataxic male, open circle = normal female, solid circle = ataxic female.
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ACKNOWLEDGEMENTS N.L. D-r-O M. These studies were supported by L'Association Canadienne de I'Ataxie de Friedreich, la Fondation Jeanne-Mance. and a Local Initiative Project. The contribution of 6 Dr. Eva Andermann for one of the kindreds is gratefully acknowledged, as well as the help of many members of La Societe de Genealogie £ Canadienne-Francaise.
REFERENCES BELL, J. M., and CARMICHAEL, E. A. U (1939). On hereditary ataxia and spastic paraplegia. In: Treasury of Human Inheri tance, Vol. 4, Cambridge Press, London, pp. 141-284. SCHUT, J. W. (1950). Hereditary ataxia: Clinical study through 6 generations. Arch. D-r
Figure 3 — Possible links between kindreds A and D with Friedreich's ataxia in French Canada. Open square = normal male, solid square = ataxic male, open circle = normal female, solid circle = ataxic female.
M.C D—r—O S.V. 1
£53*5511 KINDRED -C KINDRED-D
KINDRED-A KINDRED-B
Figure 4 —One of 10 possible pairs of common ancestors to the 4 studied kindreds with Friedreich's ataxia in French Canada. Open square = normal male, solid square = ataxic male, open circle = normal female, solid circle = ataxic female.
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