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

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

Research output: Contribution to journalArticle

101 Citations (Scopus)

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 θ=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.

Original languageEnglish
Pages (from-to)2720-2723
Number of pages4
JournalCirculation
Volume109
Issue number22
Early online date1 Jun 2004
DOIs
Publication statusPublished - 8 Jun 2004
Externally publishedYes

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Chromosomes
Mutation
Genes
Inheritance Patterns
X-Linked Genes
Genetic Heterogeneity
Genetic Testing
Human Chromosomes
Cardiomyopathies
Morphogenesis
Haplotypes
Heart Diseases
Myocardium
Genome

Cite this

Sasse-Klaassen, S., Probst, S., Gerull, B., Oechslin, E., Nürnberg, P., Heuser, A., ... Thierfelder, L. (2004). Novel Gene Locus for Autosomal Dominant Left Ventricular Noncompaction Maps to Chromosome 11p15. Circulation, 109(22), 2720-2723. https://doi.org/10.1161/01.CIR.0000131865.21260.56
Sasse-Klaassen, Sabine ; Probst, Susanne ; Gerull, Brenda ; Oechslin, Erwin ; Nürnberg, Peter ; Heuser, Arnd ; Jenni, Rolf ; Hennies, Hans Christian ; Thierfelder, Ludwig. / Novel Gene Locus for Autosomal Dominant Left Ventricular Noncompaction Maps to Chromosome 11p15. In: Circulation. 2004 ; Vol. 109, No. 22. pp. 2720-2723.
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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 θ=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.",
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Sasse-Klaassen, S, Probst, S, Gerull, B, Oechslin, E, Nürnberg, P, Heuser, A, Jenni, R, Hennies, HC & Thierfelder, L 2004, 'Novel Gene Locus for Autosomal Dominant Left Ventricular Noncompaction Maps to Chromosome 11p15', Circulation, vol. 109, no. 22, pp. 2720-2723. https://doi.org/10.1161/01.CIR.0000131865.21260.56

Novel Gene Locus for Autosomal Dominant Left Ventricular Noncompaction Maps to Chromosome 11p15. / Sasse-Klaassen, Sabine; Probst, Susanne; Gerull, Brenda; Oechslin, Erwin; Nürnberg, Peter; Heuser, Arnd; Jenni, Rolf; Hennies, Hans Christian; Thierfelder, Ludwig.

In: Circulation, Vol. 109, No. 22, 08.06.2004, p. 2720-2723.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Novel Gene Locus for Autosomal Dominant Left Ventricular Noncompaction Maps to Chromosome 11p15

AU - Sasse-Klaassen, Sabine

AU - Probst, Susanne

AU - Gerull, Brenda

AU - Oechslin, Erwin

AU - Nürnberg, Peter

AU - Heuser, Arnd

AU - Jenni, Rolf

AU - Hennies, Hans Christian

AU - Thierfelder, Ludwig

PY - 2004/6/8

Y1 - 2004/6/8

N2 - 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 θ=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.

AB - 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 θ=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.

KW - Cardiomyopathy

KW - Genetics

KW - Mapping

KW - Noncompaction

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U2 - 10.1161/01.CIR.0000131865.21260.56

DO - 10.1161/01.CIR.0000131865.21260.56

M3 - Article

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SP - 2720

EP - 2723

JO - Circulation

JF - Circulation

SN - 0009-7322

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Sasse-Klaassen S, Probst S, Gerull B, Oechslin E, Nürnberg P, Heuser A et al. Novel Gene Locus for Autosomal Dominant Left Ventricular Noncompaction Maps to Chromosome 11p15. Circulation. 2004 Jun 8;109(22):2720-2723. https://doi.org/10.1161/01.CIR.0000131865.21260.56