title: Homozygous mutation of desmocollin-2 in arrhythmogenic right ventricular cardiomyopathy with mild palmoplantar keratoderma and woolly hair.
abstract: OBJECTIVE
  The phenotypic triad of arrhythmogenic right ventricular cardiomyopathy (ARVC) associated with palmoplantar keratoderma and woolly hair has been previously associated with homozygous mutations in both plakoglobin and desmoplakin, which are both critical components of the desmosome. We present here a clinical and genetic study of a consanguineous pedigree in which 2 siblings present with ARVC with left ventricular involvement and associated mild palmoplantar keratoderma and woolly hair.
  
  
  METHODS
  Clinical evaluation of the 2 patients and their family members was undertaken along with a homozygosity-mapping approach to identify the relevant gene and sequencing analysis to identify the causative mutation.
  
  
  RESULTS
  The homozygosity-mapping approach excluded the involvement of both plakoglobin and desmoplakin in this pedigree. However, an extended region of homozygosity in both affected cases was revealed at the chromosome 18 desmocollin/desmoglein cluster, genes which encode components of the desmosome. Sequence analysis of the democollin-2 gene, located within this cluster, revealed a homozygous single-base deletion in exon 12 (1841delG). This mutation is predicted to lead to a frame shift and a premature termination codon at position 625 (S614fsX625).
  
  
  CONCLUSIONS
  This is the first reported case of a mutation in desmocollin-2 associated with autosomal recessive ARVC.
authors.affiliation: Medical Genetics, Clinical Developmental Sciences, St George's University of London, London, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Simpson
authors.forename: S
authors.initials: S
authors.lastname: Mansour
authors.forename: D
authors.initials: D
authors.lastname: Ahnood
authors.forename: K
authors.initials: K
authors.lastname: Kalidas
authors.forename: M A
authors.initials: MA
authors.lastname: Patton
authors.forename: W J
authors.initials: WJ
authors.lastname: McKenna
authors.forename: E R
authors.initials: ER
authors.lastname: Behr
authors.forename: A H
authors.initials: AH
authors.lastname: Crosby
mesh_terms: D000328:Adult; D000368:Aged; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics* / Q000378:metabolism; D051187:Desmocollins / Q000235:genetics*; D003896:Desmosomes / Q000378:metabolism*; D005260:Female; D005808:Genes, Recessive; D006197:Hair; D006720:Homozygote; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010375:Pedigree
chemical_list: C081561:DSC2 protein, human; D051187:Desmocollins