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Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin
- McAleer, Maeve A;
- Pohler, Elizabeth;
- Smith, Frances JD;
- Wilson, Neil J;
- Cole, Christian;
- MacGowan, Stuart;
- Koetsier, Jennifer L;
- Godsel, Lisa M;
- Harmon, Robert M;
- Gruber, Robert;
- Crumrine, Debra;
- Elias, Peter M;
- McDermott, Michael;
- Butler, Karina;
- Broderick, Annemarie;
- Sarig, Ofer;
- Sprecher, Eli;
- Green, Kathleen J;
- McLean, WH Irwin;
- Irvine, Alan D
- et al.
Published Web Location
https://doi.org/10.1016/j.jaci.2015.05.002Abstract
Background
Severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 gene (DSG1). To date, only 3 families have been reported.Objective
We studied a new case of SAM syndrome known to have no mutations in DSG1 to detail the clinical, histopathologic, immunofluorescent, and ultrastructural phenotype and to identify the underlying molecular mechanisms in this rare genodermatosis.Methods
Histopathologic, electron microscopy, and immunofluorescent studies were performed. Whole-exome sequencing data were interrogated for mutations in desmosomal and other skin structural genes, followed by Sanger sequencing of candidate genes in the patient and his parents.Results
No mutations were identified in DSG1; however, a novel de novo heterozygous missense c.1757A>C mutation in the desmoplakin gene (DSP) was identified in the patient, predicting the amino acid substitution p.His586Pro in the desmoplakin polypeptide.Conclusions
SAM syndrome can be caused by mutations in both DSG1 and DSP. Knowledge of this genetic heterogeneity is important for both analysis of patients and genetic counseling of families. This condition and these observations reinforce the importance of heritable skin barrier defects, in this case desmosomal proteins, in the pathogenesis of atopic disease.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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