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Original Contribution
February 2007

Three Families With Amyotrophic Lateral Sclerosis and Frontotemporal Dementia With Evidence of Linkage to Chromosome 9p

Author Affiliations

Author Affiliations: Center for the Study of Brain Diseases, University of Montreal, Centre Hospitalier de l’Université de Montréal (CHUM) Research Center, Notre-Dame Hospital (Mr Valdmanis and Drs Dupre and Rouleau) and Department of Human Genetics, McGill University (Mr Valdmanis), Montreal, Quebec; Department of Neurological Sciences, Centre Hospitalier Affilié Universitaire de Québec (CHAUQ), Hôpital de l’Enfant-Jésus, Quebec City, Quebec (Drs Dupre and Bouchard); Unité de Neurologie Comportementale et Dégénérative Molecular Unit, Institute of Biology, and Clinique du Motoneurone, Service d'Explorations Neurologiques, Hôpital Guy de Chauliac, Montpellier, France (Dr Camu); Fédération des Maladies du Système Nerveux, Division Paul Castaigne, Hôpital de la Salpêtrière, Paris, France (Drs Salachas and Meininger); and Department of Clinical Neurological Sciences, University of Western Ontario, London (Dr Strong).

Arch Neurol. 2007;64(2):240-245. doi:10.1001/archneur.64.2.240

Background  Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with adult onset that generally progress rapidly after the onset of symptoms. The 2 conditions are independent, but they also overlap in a significant proportion of families, including 2 families in which the disorders are reported to be linked to chromosome 9p. A locus was established between the markers D9S2154 and D9S1791 by comparing haplotypes between these families.

Objective  To determine whether additional families have ALS and FTD linked to chromosome 9p.

Methods  Families were identified in Canada and France, and genotyping was performed using sequence tagged site markers around the ALS-FTD candidate interval.

Results  Three new families with mapping to the chromosome 9p ALS-FTD locus were identified. Analysis of the largest family shows a peak 2-point logarithm of odds (LOD) score of 2.81 and a multipoint LOD score of 3.01. The particular candidate interval delineated by this family spans 27.1 centimorgans (cM) between markers D9S157 and D9S1805. This reduces the centromeric boundary of the candidate interval compared with previously reported values, shortening the locus to 8.1 cM (8.0 megabase pairs). A maximum multipoint LOD score of 7.22 is obtained when the 3 families are combined.

Conclusions  The identification of new families enables reduction of the ALS-FTD candidate region located on chromosome 9p. The clinical features observed in these families help characterize the profiles of ALS and FTD with linkage to chromosome 9p–linked families.