Journal
GENOMICS
Volume 99, Issue 4, Pages 202-208Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2012.01.005
Keywords
Genodermatosis; Whole-exome; Mutation; Epidermis; Carbohydrate-sulfotransferase
Funding
- USPHS/NIH from NIAMS [RO1AR44924]
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Generalized peeling skin syndrome (PSS) is an autosomal recessive genodermatosis characterized by lifelong, continuous shedding of the upper epidermis. Using whole-genome homozygozity mapping and whole-exome sequencing, we identified a novel homozygous missense mutation (c.229C>T, R77W) within the CHST8 gene, in a large consanguineous family with non-inflammatory PSS type A. CHST8 encodes a Golgi transmembrane N-acetylgalactosamine-4-O-sulfotransferase (GaINAc4-ST1), which we show by immunofluorescence staining to be expressed throughout normal epidermis. A colorimetric assay for total sulfated glycosaminoglycan (GAG) quantification, comparing human keratinocytes (CCD1106 KERTr) expressing wild type and mutant recombinant GaINAc4-ST1, revealed decreased levels of total sulfated GAGs in cells expressing mutant GaINAc4-ST1, suggesting loss of function. Western blotting revealed lower expression levels of mutant recombinant GaINAc4-ST1 compared to wild type, suggesting that accelerated degradation may result in loss of function, leading to PSS type A. This is the first report describing a mutation as the cause of PSS type A. (C) 2012 Elsevier Inc. All rights reserved.
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