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

Circulation. 2004 Jun 8;109(22):2720-3. doi: 10.1161/01.CIR.0000131865.21260.56. Epub 2004 Jun 1.

Abstract

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 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.

MeSH terms

  • Adolescent
  • Cardiomyopathies / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 11*
  • DNA-Binding Proteins / genetics
  • Female
  • Genes, Dominant
  • Haplotypes
  • High Mobility Group Proteins / genetics
  • Humans
  • LIM Domain Proteins
  • Lod Score
  • Male
  • Muscle Proteins / genetics
  • Mutation
  • Pedigree
  • SOXD Transcription Factors
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • LIM Domain Proteins
  • Muscle Proteins
  • SOX6 protein, human
  • SOXD Transcription Factors
  • Transcription Factors
  • cysteine and glycine-rich protein 3

Associated data

  • OMIM/604169