Heart–hand syndrome of Slovenian type: a new kind of laminopathy
- L Renou1,2,
- S Stora1,2,
- R Ben Yaou1,2,
- M Volk3,
- M Šinkovec4,
- L Demay5,
- P Richard1,2,5,
- B Peterlin3,
- G Bonne1,2,5
- 1Inserm, U582, Paris, France
- 2UPMC Univ Paris 06, UMR_S582, Institut de Myologie, IFR14, Paris, France
- 3Division of Medical Genetics, Department Obstetrics and Gynecology, University Medical Center Ljubljana, Ljubljana, Slovenia
- 4Department of Cardiology, University Medical Center Ljubljana, Ljubljana, Slovenia
- 5AP-HP, Groupe Hospitalier Pitié-Salpêtrière, U.F. Cardiogénétique et Myogénétique, Service de Biochimie Métabolique, Paris, France
- Dr G Bonne, Inserm U582-Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, 47 boulevard de l’Hôpital, 75651 Paris cedex 13, France;
- Received 24 April 2008
- Revised 13 June 2008
- Accepted 19 June 2008
- Published Online First 8 July 2008
Background: Heart–hand syndromes are a heterogeneous group of genetic disorders characterised by the association of congenital cardiac disease and limb deformities. Laminopathies are a group of diseases caused by mutations in the LMNA gene encoding A-type lamins.
Results: We report a new LMNA mutation (c.1609-12T>G, IVS9-12 T>G) that creates a new cryptic splicing site with the retention of 11 intronic nucleotides in the mRNA. This LMNA mutation segregates with a new type of heart–hand syndrome in a previously reported family suffering from adult onset progressive conduction system disease, atrial and ventricular tachyarrhythmias, sudden death, dilated cardiomyopathy, and brachydactyly with predominant foot involvement. Analysis of the fibroblasts of two affected family members identified for the first time a truncated lamin A/C protein resulting from the frame shift created by the new splicing site, together with nuclear envelope abnormalities confirming that this LMNA mutation is pathogenic.
Conclusions: This new heart–hand syndrome should therefore be considered as a new kind of laminopathy. As part of laminopathies with heart involvement, patients presenting with this phenotype and their relatives are at risk for developing sudden cardiac death and should beneficiate from appropriate LMNA genetic diagnosis.
Funding: This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique-Hôpitaux de Paris (AP-HP), Association Française contre les Myopathies (AFM) rare disorder network program (10722), and European Union Fifth Framework (Euro-laminopathies contract 018690).
Competing interests: None.
Patient consent: Obtained.