RT Journal Article
SR Electronic
T1 Heart–hand syndrome of Slovenian type: a new kind of laminopathy
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 666
OP 671
DO 10.1136/jmg.2008.060020
VO 45
IS 10
A1 Renou, L
A1 Stora, S
A1 Yaou, R Ben
A1 Volk, M
A1 Šinkovec, M
A1 Demay, L
A1 Richard, P
A1 Peterlin, B
A1 Bonne, G
YR 2008
UL http://jmg.bmj.com/content/45/10/666.abstract
AB 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.