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A Novel Locus for Dilated Cardiomyopathy, Diffuse Myocardial Fibrosis, and Sudden Death on Chromosome 10q25-26

Patrick T. Ellinor, MD, PhD^_*,, Sabine Sasse-Klaassen, MD, Susanne Probst, MSc, Brenda Gerull, MD, Jordan T. Shin, MD, PhD^_*,, Andrea Toeppel, PhD, Arnd Heuser, MD, Beate Michely, MD, Danita M. Yoerger, MD, Bong-Seok Song, MD, Bernhard Pilz, MD^||, Gregor Krings, MD^¶, Bruce Coplin, MD^_**, Peter E. Lange, MD, G. William Dec, MD, Hans Christian Hennies, PhD, Ludwig Thierfelder, MD^,||, and Calum A. MacRae, MB, ChB, PhD^_*,,_*

^_* Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts
Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts
Max-Delbrueck Center for Molecular Medicine, Berlin, Germany
Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts
^|| Franz-Volhard Clinic, HELIOS Clinics GmbH, Charité, Humboldt University Berlin, Berlin, Germany
^¶ Clinic for Pediatrics, Cardiology Division, Charité, Humboldt University Berlin, Berlin, Germany
^_** Albany Associates in Cardiology, Albany, New York
Department of Congenital Heart Disease, German Heart Institute Berlin, Berlin, Germany
Cologne Center for Genomics, Cologne, Germany.

View larger version (35K): [in a new window]   Figure 1 Pedigrees and haplotypes for families DCM-50 (A) and DCM-100 (B). Black symbols indicate individuals with cardiomyopathy; open symbols, unaffected status; and hatched symbols, unknown/indeterminate clinical status. The marker order from centromere to telomere is listed on the left of the figure, and the minimum disease haplotype for each family is enclosed in a box.

View larger version (180K): [in a new window]   Figure 2 Sirius red-stained histologic section from the left ventricle of individual V-4, family CM100. Connective tissue is evident as an intense red staining throughout the interstitium.

View larger version (15K): [in a new window]   Figure 3 Multipoint logarithm of the odds (LOD) score curve. The multipoint LOD score is plotted on the abscissa, whereas the recombination distance () is plotted on the ordinate in centiMorgans (cM) from an arbitrary origin set at marker D10S521.

View larger version (14K): [in a new window]   Figure 4 Ideogram of chromosome 10. The known loci and genes for dilated cardiomyopathy on chromosome 10 are illustrated. For a high-resolution map of this region, please also see the UCSC Human Genome Browser.