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(Circulation. 2004;109:2720-2723.)
© 2004 American Heart Association, Inc.

Brief Rapid Communications

Novel Gene Locus for Autosomal Dominant Left Ventricular Noncompaction Maps to Chromosome 11p15

Sabine Sasse-Klaassen, MD; Susanne Probst, MSc; Brenda Gerull, MD; Erwin Oechslin, MD; Peter Nürnberg, PhD; Arnd Heuser, MD; Rolf Jenni, MD; Hans Christian Hennies, PhD; Ludwig Thierfelder, MD

From the Max-Delbrück-Center for Molecular Medicine (S.S.-K., S.P., B.G., A.H., L.T.) and the Gene Mapping Center, Max-Delbrück-Center for Molecular Medicine (P.N., H.C.H.), Berlin, Germany; Cardiovascular Center, Division of Echocardiography, University Hospital Zürich, Zürich, Switzerland (E.O., R.J.); and Institute of Medical Genetics (P.N.) and Franz-Volhard-Clinic, Helios Clinic (L.T.), Charité, Humboldt University Berlin, Berlin, Germany.

Correspondence to Sabine Sasse-Klaassen, MD, Max Delbrück Center for Molecular Medicine, Robert-Roessle Str 10, 13092 Berlin, Germany. E-mail sasse{at}mdc-berlin.de

Received February 17, 2004; revision received April 6, 2004; accepted April 27, 2004.

Background— Left ventricular noncompaction (LVNC) is a congenital unclassified cardiomyopathy with numerous prominent trabeculations and deep intertrabecular recesses in a hypertrophied and hypokinetic myocardium. It has been reported to occur in isolation or in association with congenital heart disease. Mutations in the X-linked G4.5 gene are responsible for cases of isolated LVNC in male infants, but G4.5 mutations were not found in patients with clinical onset of disease in adulthood. In addition, several families with LVNC and an autosomal dominant pattern of inheritance suggest genetic heterogeneity.

Methods and Results— We performed a genome-wide linkage analysis in a family with autosomal dominant LVNC and show that a locus containing the LVNC disease gene maps to chromosome 11p15. A peak 2-point logarithm of odds score of 5.06 was obtained with marker D11S902 at =0. Haplotype analysis defined a critical interval of 6.4 centimorgan between D11S1794 and D11S928 corresponding to a physical distance of 6.8 megabases. No disease-causing mutation was identified in 2 prime positional candidate genes, muscle LIM protein (MLP) and SOX6.

Conclusions— We have mapped a locus for autosomal dominant LVNC to a 6.8-megabase region on human chromosome 11p15. Identification of the disease gene will allow genetic screening and provide fundamental insight into the understanding of myocardial morphogenesis.

Key Words: cardiomyopathy • genetics • mapping • noncompaction

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