Homozygous Mutation of Desmocollin-2 in Arrhythmogenic Right Ventricular Cardiomyopathy with Mild Palmoplantar Keratoderma and Woolly HairSimpson M.A.a · Mansour S.a · Ahnood D.a · Kalidas K.a · Patton M.A.a · McKenna W.J.c · Behr E.R.b · Crosby A.H.a
aMedical Genetics, Clinical Developmental Sciences, and bCardiac and Vascular Sciences, St George’s University of London, cDepartment of Medicine, University College London and The Heart Hospital, University College Hospitals Trust, London, UK
Objectives: 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.
© 2008 S. Karger AG, Basel
E.R.B and A.H.C. contributed equally to the manuscript.
Received: May 21, 2008
Accepted after revision: June 14, 2008
Published online: October 29, 2008
Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 1, Number of References : 28
Cardiology (International Journal of Cardiovascular Medicine, Surgery, Pathology and Pharmacology)
Vol. 113, No. 1, Year 2009 (Cover Date: March 2009)
Journal Editor: Borer J.S. (New York, N.Y.)
ISSN: 0008–6312 (Print), eISSN: 1421–9751 (Online)
For additional information: http://www.karger.com/CRD