title: Two Novel Homozygous Desmoplakin Mutations in Carvajal Syndrome.
abstract: BACKGROUND
  Mutations in various desmosomal proteins were shown to cause inherited forms of cardiomyopathy. Carvajal syndrome (Online Mendelian Inheritance in Man [OMIM] 605676) is characterized by the association of dilated cardiomyopathy, striate palmoplantar keratoderma, and woolly hair. It is caused by homozygous as well as heterozygous mutations in DSP, which encodes the desmosomal plaque protein desmoplakin. An overlapping cardiocutaneous phenotype was also described with homozygous mutations in genes encoding two other desmosomal proteins; plakoglobin (Naxos disease; OMIM 601214) and desmocollin-2 (OMIM 610476).
  
  
  METHODS
  We performed clinical and molecular workups in two consanguineous Arab Palestinian families manifesting an autosomal recessive pattern of inheritance of the above mentioned clinical findings. Whole exome sequencing was employed in the search for the causing mutation.
  
  
  RESULTS
  Affected family members suffered from biventricular involvement and arrhythmogenic right ventricular dysplasia based on echocardiography and magnetic resonance imaging. One patient who underwent implantation of an implantable cardioverter-defibrillator (ICD) is still alive at the age of 59 years. Whole exome sequencing revealed two novel homozygous mutations in DSP, each affecting one family.
  
  
  CONCLUSIONS
  The association of woolly hair with palmoplantar keratoderma in a child should lead to a cardiac workup in the search for those at increased risk for sudden cardiac death. Early diagnosis and ICD implantation may be lifesaving. Whole exome sequencing should be utilized for rapid genetic analysis since the cardiocutaneous phenotype may result from mutations in one of several genes.
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.|Center for Genetic Diseases of the Skin and Hair, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Vered
authors.initials: V
authors.lastname: Molho-Pessach
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Sivan
authors.initials: S
authors.lastname: Sheffer
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Rula
authors.initials: R
authors.lastname: Siam
authors.affiliation: Faculty of Medicine, Palestinian Al Quds University, Abu Dis, Palestinian Authority.
authors.forename: Spiro
authors.initials: S
authors.lastname: Tams
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Ihab
authors.initials: I
authors.lastname: Siam
authors.affiliation: Caritas Baby Hospital, Bethlehem, Palestinian Authority.
authors.forename: Rula
authors.initials: R
authors.lastname: Awwad
authors.affiliation: Center for Genetic Diseases of the Skin and Hair, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Sofia
authors.initials: S
authors.lastname: Babay
authors.affiliation: Department of Pediatric Cardiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Julius
authors.initials: J
authors.lastname: Golender
authors.affiliation: Department of Medical Imaging, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Natalia
authors.initials: N
authors.lastname: Simanovsky
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.|Center for Genetic Diseases of the Skin and Hair, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Ramot
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.|Center for Genetic Diseases of the Skin and Hair, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Zlotogorski
mesh_terms: D000293:Adolescent; D009202:Cardiomyopathies / Q000235:genetics*; D002311:Cardiomyopathy, Dilated; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D051180:Desmoplakins / Q000235:genetics*; D005820:Genetic Testing; D006201:Hair Diseases / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D055815:Young Adult
chemical_list: C495294:DSP protein, human; D051180:Desmoplakins