title: Heart-hand syndrome of Slovenian type: a new kind of laminopathy.
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.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.
authors.forename: L
authors.initials: L
authors.lastname: Renou
authors.forename: S
authors.initials: S
authors.lastname: Stora
authors.forename: R Ben
authors.initials: RB
authors.lastname: Yaou
authors.forename: M
authors.initials: M
authors.lastname: Volk
authors.forename: M
authors.initials: M
authors.lastname: Sinkovec
authors.forename: L
authors.initials: L
authors.lastname: Demay
authors.forename: P
authors.initials: P
authors.lastname: Richard
authors.forename: B
authors.initials: B
authors.lastname: Peterlin
authors.forename: G
authors.initials: G
authors.lastname: Bonne
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D016368:Frameshift Mutation; D006330:Heart Defects, Congenital / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D017880:Limb Deformities, Congenital / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000737:chemistry
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D022821:RNA Splice Sites; D012333:RNA, Messenger