Author/Editor		Renou, L; Stora, S; Ben Yaou, R; Volk, M; Šinkovec, M; Demay, L; Richard, P; Peterlin, B; Bonne, G
Title		Heart-hand syndrome of Slovenian type: a new kind of laminopathy
Type		članek
Source		J Med Genet
Vol. and No.		Letnik 45
Publication year		2010
Volume		str. 666-71
Language		eng
Abstract		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.160912T>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 AlG 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 sud den cardiac death and should beneficiate from appropriate LMNA genetic diagnosis.
Descriptors		HEART DEFECTS, CONGENITAL HAND DEFORMITIES, CONGENITAL NUCLEAR MATRIX MUTATION ELECTROMYOGRAPHY ELECTROCARDIOGRAPHY PEDIGREE FIBROBLASTS CELLS, CULTURED POLYMERASE CHAIN REACTION FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT SLOVENIA