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Heart-hand syndrome of Slovenian type: a new kind of laminopathy
  1. Laure Renou (g.bonne{at}institut-myologie.org)
  1. Inserm, U582, Institut de Myologie, UPMC Univ Paris 06, UMR_S582, IFR14, Paris, France
    1. Samantha Stora (samantha.stora{at}mail.ap-hm.fr)
    1. Inserm, U582, Institut de Myologie, UPMC Univ Paris 06, UMR_S582, IFR14, Paris, France
      1. Rabah Ben Yaou (r.benyaou{at}institut-myologie.org)
      1. Inserm, U582, Institut de Myologie, UPMC Univ Paris 06, UMR_S582, IFR14, Paris, France
        1. Marija Volk (marija.volk{at}medicinska-genetika.com)
        1. Division of Med Genetics, Dpt. Obstetrics and Gynecology, Univ Medical Center, Ljubljana, Slovenia
          1. Matjaz Šinkovec (matjaz.sinkovec{at}kclj.si)
          1. Department of Cardiology, University Medical Center Ljubljana, Ljubljana, Slovenia
            1. Laurence Demay (pascale.richard{at}psl.aphp.fr)
            1. AP-HP, GH Pitié-Salpêtrière, U.F. Myogénétique et Cardiogén, France
              1. Pascale Richard (pascale.richard{at}psl.aphp.fr)
              1. AP-HP, GH Pitié-Salpêtrière, U.F. Myogénétique et Cardiogén, France
                1. Borut Peterlin (borut.peterlin{at}guest.arnes.si)
                1. Division of Med Genetics, Dpt. Obstetrics and Gynecology, Univ Medical Center, Ljubljana, Slovenia
                  1. Gisèle Bonne (g.bonne{at}institut-myologie.org)
                  1. Inserm, U582, Institut de Myologie, UPMC Univ Paris 06, UMR_S582, IFR14, Paris, France

                    Abstract

                    Background: Heart-hand syndromes are a heterogeneous group of genetic disorders characterized 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 2 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. And 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.

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