Novel gene locus for autosomal dominant left ventricular noncompaction maps to chromosome 11p15

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. Mutati...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2004-06, Vol.109 (22), p.2720-2723
Main Authors: SASSE-KLAASSEN, Sabine, PROBST, Susanne, GERULL, Brenda, OECHSLIN, Erwin, NÜRNBERG, Peter, HEUSER, Arnd, JENNI, Rolf, HENNIES, Hans Christian, THIERFELDER, Ludwig
Format: Article
Language:English
Subjects:
Adolescent
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Cardiomyopathies - genetics
Cardiovascular system
Chromosome Mapping
Chromosomes, Human, Pair 11
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
DNA-Binding Proteins - genetics
Female
Genes, Dominant
Haplotypes
High Mobility Group Proteins - genetics
Humans
LIM Domain Proteins
Lod Score
Male
Medical sciences
Muscle Proteins - genetics
Mutation
Pedigree
Pharmacology. Drug treatments
SOXD Transcription Factors
Transcription Factors - genetics
Vasodilator agents. Cerebral vasodilators
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Summary: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. 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 theta=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. 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.
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.0000131865.21260.56