LETTER TO JMG

Heart–hand syndrome of Slovenian type: a new kind of laminopathy

L Renou^1,2, S Stora^1,2, R Ben Yaou^1,2, M Volk³, M inkovec⁴, L Demay⁵, P Richard^1,2,5, B Peterlin³, G Bonne^1,2,5

¹ Inserm, U582, Paris, France
² UPMC Univ Paris 06, UMR_S582, Institut de Myologie, IFR14, Paris, France
³ Division of Medical Genetics, Department Obstetrics and Gynecology, University Medical Center Ljubljana, Ljubljana, Slovenia
⁴ Department of Cardiology, University Medical Center Ljubljana, Ljubljana, Slovenia
⁵ AP-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; g.bonne{at}institut-myologie.org

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?