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


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 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.


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.
Sasse-Klaassen
Sabine
S
Max Delbrück Center for Molecular Medicine, Robert-Roessle Str 10, 13092 Berlin, Germany. sasse@mdc-berlin.de
Probst
Susanne
S
Gerull
Brenda
B
Oechslin
Erwin
E
Nürnberg
Peter
P
Heuser
Arnd
A
Jenni
Rolf
R
Hennies
Hans Christian
HC
Thierfelder
Ludwig
L
D000293:Adolescent; D009202:Cardiomyopathies / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D006239:Haplotypes; D006609:High Mobility Group Proteins / Q000235:genetics; D006801:Humans; D060588:LIM Domain Proteins; D008126:Lod Score; D008297:Male; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D055755:SOXD Transcription Factors; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; C486270:SOX6 protein, human; D055755:SOXD Transcription Factors; D014157:Transcription Factors; C090114:cysteine and glycine-rich protein 3