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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Homozygous mutations in the 5′ region of the JUP gene result in cutaneous disease but normal heart development in children
Journal of Investigative Dermatology, Volume 130, No. 6, Year 2010
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Description
Desmosomes are intercellular adhesive junctions and attachment sites for the intermediate filament (IF) cytoskeleton, prominent in tissues subject to high levels of mechanical stress such as the epidermis and heart. The obligate desmosomal constituent, plakoglobin (PG), is involved in coupling transmembrane desmosomal components with IFs. PG also contributes to intercellular adhesion through adherens junctions and has additional signaling roles. To date, two mutations in the gene encoding PG, JUP, have been described, and in both instances, patients harboring pathogenic mutations suffered from arrhythmogenic right ventricular cardiomyopathy with or without skin abnormalities. We describe homozygous nonsense mutation, p.S24X, and homozygous splice site mutation, c.468G > A, in the JUP gene that results in skin fragility, diffuse palmoplantar keratoderma, and woolly hair with no symptoms of cardiomyopathy. We show barely detectable levels of PG immunostaining in skin sections from patients harboring these mutations and show that an alternative AUG codon in p.S24X mRNA translates a 42-amino-acid N-terminal truncation. We conclude that PG is required for correct maintenance of skin integrity, and the absence of heart phenotype in patients suggests that aberrant PG expression does not compromise normal human heart development in children. Our findings provide new insight into the distinct roles that PG has in the epidermis and heart. © 2010 The Society for Investigative Dermatology.
Authors & Co-Authors
Cabral, Rita M.
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Liu, Lu
United Kingdom, London
St Thomas' Hospital
Hogan, Carol
United Kingdom, Dundee
University of Dundee School of Medicine
Dopping-Hepenstal, Patricia J.C.
United Kingdom, London
St Thomas' Hospital
Winik, Beatriz C.
Argentina, San Miguel de Tucuman
Instituto Superior de Investigaciones Biologicas
Asial, Raúl A.
Argentina, San Miguel de Tucuman
Universidad Nacional de Tucuman Unt
Dobson, Richard J.B.
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Mein, Charles A.
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Baselaga, Patricia A.
Argentina, San Miguel de Tucuman
Niño Jesús Children's Hospital
Mellerio, Jemima Elizabeth
United Kingdom, London
St John's Institute of Dermatology
Nanda, Arti
Kuwait, Kuwait City
As'ad Al-hamad Dermatology Center
del Carmen Boente, María
Argentina, San Miguel de Tucuman
Hospital Del Niño Jesus, Argentina
Kelsell, David Peter
United Kingdom, London
Barts and the London School of Medicine and Dentistry
McGrath, J. A.
United Kingdom, London
St John's Institute of Dermatology
South, Andrew P.
United Kingdom, London
Barts and the London School of Medicine and Dentistry
United Kingdom, Dundee
University of Dundee School of Medicine
Statistics
Citations: 54
Authors: 15
Affiliations: 9
Identifiers
Doi:
10.1038/jid.2010.7
ISSN:
0022202X
e-ISSN:
15231747
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health