title: Novel desmoplakin mutation: juvenile biventricular cardiomyopathy with left ventricular non-compaction and acantholytic palmoplantar keratoderma.
abstract: Two sons of a consanguineous marriage developed biventricular cardiomyopathy. One boy died of severe heart failure at the age of 6 years, the other was transplanted because of severe heart failure at the age of 10 years. In addition, focal palmoplantar keratoderma and woolly hair were apparent in both boys. As similar phenotypes have been described in Naxos disease and Carvajal syndrome, respectively, the genes for plakoglobin (JUP) and desmoplakin (DSP) were screened for mutations using direct genomic sequencing. A novel homozygous 2 bp deletion was identified in an alternatively spliced region of DSP. The deletion 5208_5209delAG led to a frameshift downstream of amino acid 1,736 with a premature truncation of the predominant cardiac isoform DSP-1. This novel homozygous truncating mutation in the isoform-1 specific region of the DSP C-terminus caused Carvajal syndrome comprising severe early-onset heart failure with features of non-compaction cardiomyopathy, woolly hair and an acantholytic form of palmoplantar keratoderma in our patient. Congenital hair abnormality and manifestation of the cutaneous phenotype in toddler age can help to identify children at risk for cardiac death.
authors.affiliation: Department of Internal Medicine I, Center of Cardiovascular Medicine, University Hospital of Wuerzburg, Wuerzburg, Germany. williams_t@klinik.uni-wuerzburg.de
authors.forename: Tatjana
authors.initials: T
authors.lastname: Williams
authors.forename: Wolfram
authors.initials: W
authors.lastname: Machann
authors.forename: Leif
authors.initials: L
authors.lastname: Kühler
authors.forename: Henning
authors.initials: H
authors.lastname: Hamm
authors.forename: Josef
authors.initials: J
authors.lastname: Müller-Höcker
authors.forename: Michael
authors.initials: M
authors.lastname: Zimmer
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Oliver
authors.initials: O
authors.lastname: Ritter
authors.forename: Meinrad
authors.initials: M
authors.lastname: Beer
authors.forename: Jost
authors.initials: J
authors.lastname: Schönberger
mesh_terms: D017668:Age of Onset; D001483:Base Sequence; D009202:Cardiomyopathies / Q000175:diagnosis / Q000235:genetics*; D002311:Cardiomyopathy, Dilated; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D051180:Desmoplakins / Q000235:genetics*; D017809:Fatal Outcome; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D006201:Hair Diseases / Q000175:diagnosis / Q000235:genetics*; D006333:Heart Failure / Q000235:genetics; D006720:Homozygote; D006801:Humans; D056830:Isolated Noncompaction of the Ventricular Myocardium / Q000175:diagnosis / Q000235:genetics*; D007645:Keratoderma, Palmoplantar / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D017384:Sequence Deletion; D012720:Severity of Illness Index
chemical_list: C495294:DSP protein, human; D051180:Desmoplakins