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From Day Neuromuscular Laboratory (M.M., A.A.-C., P.M.A., B.H., P.S., J.X., W.J., R.H.B.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (A.A.-C.), King’s College London, Institute of Psychiatry, UK; Department of Neurology (P.M.A.), Umeå University Hospital and Institute of Clinical Neuroscience, Umeå University, Sweden; Howard Hughes Medical Institute (P.S., H.R.H.), Department of Biology, Massachusetts Institute of Technology, Cambridge; Department of Pathology (E.E.), Lund University Hospital, Sweden; Faculty of Medicine (J.E.M., J.J.H., J.d.B.), Imperial College London, Charing Cross Hospital, UK; and Department of Clinical Medicine (L.-G.G.), Örebro University Hospital, Örebro University, Sweden.
Address correspondence and reprint requests to Dr Brown, Jr., Day Neuromuscular Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129; e-mail: BrownRHJr{at}aol.com
Objective: To perform genetic linkage analysis in a family affected with ALS and frontotemporal dementia (FTD).
Methods: The authors performed a genome-wide linkage analysis of a four-generation, 50-member Scandinavian family in which five individuals were diagnosed with ALS and nine with FTD. Linkage calculations assuming autosomal dominant inheritance of a single neurodegenerative disease manifesting as either ALS or FTD with age-dependent penetrance were performed. Further analyses for ALS alone and FTD alone were performed. A parametric logarithm of odds (lod) score of 2.0 or greater was required for further study of a potential locus and crossover (haplotype) analysis.
Results: A new ALS-FTD locus was identified between markers D9s1870 and D9s1791 on human chromosome 9p21.3-p13.3. A maximum multipoint lod score of 3.00 was obtained between markers D9s1121 and D9s2154. Crossover analysis indicates this region covers approximately 21.8 cM, or 14Mb.
Conclusions: A locus on chromosome 9p21.3-p13.3 is linked to ALS-FTD.
This article was previously published in electronic format as an Expedited E-Pub on January 18, 2006, at www.neurology.org.
Supported by the Bengt Björklund ALS Research Foundation of the Swedish Medical Society (P.M.A.), the ALS-Huntington Disease Research Foundation (P.M.A.), the Swedish Brain Research Foundation, the Hållstens Brain Research Foundation (P.M.A.), the Angel Fund for ALS Research (R.H.B.), Project ALS (R.H.B.), the Muscular Dystrophy Association (R.H.B.), the Amyotrophic Lateral Sclerosis Association (R.H.B.), the Pierre de Bourgknecht ALS Research Foundation (R.H.B.), NIH grants 1PO1NS31248-02 (R.H.B.) and RO1NS37912 (R.H.B.), and the Howard Hughes Medical Institute (H.R.H.). H.R.H. is an Investigator of the Howard Hughes Medical Institute. At the time of this work, A.A.C. was a Medical Research Council (UK) Clinician Scientist Fellow.
Disclosure: The authors report no conflicts of interest.
Received August 1, 2005. Accepted in final form November 30, 2005.
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