Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin. McAleer, M. A.; Pohler, E.; Smith, F. J. D.; Wilson, N. J.; Cole, C.; MacGowan, S.; Koetsier, J. L.; Godsel, L. M.; Harmon, R. M.; Gruber, R.; Crumrine, D.; Elias, P. M.; McDermott, M.; Butler, K.; Broderick, A.; Sarig, O.; Sprecher, E.; Green, K. J.; McLean, W. H. I.; and Irvine, A. D. Journal of Allergy and Clinical Immunology, 136(5):1268–1276, November, 2015.
Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin [link]Paper  doi  abstract   bibtex   
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\textbackslashtextgreaterC 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.
@article{mcaleer_severe_2015,
	title = {Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the {N}-terminal plakin domain of desmoplakin},
	volume = {136},
	issn = {0091-6749, 1097-6825},
	url = {http://www.jacionline.org/article/S0091674915006533/abstract},
	doi = {10.1016/j.jaci.2015.05.002},
	abstract = {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{\textbackslash}textgreaterC 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.},
	language = {English},
	number = {5},
	urldate = {2016-03-21},
	journal = {Journal of Allergy and Clinical Immunology},
	author = {McAleer, Maeve A. and Pohler, Elizabeth and Smith, Frances J. D. and Wilson, Neil J. and Cole, Christian and MacGowan, Stuart and Koetsier, Jennifer L. and Godsel, Lisa M. and Harmon, Robert M. and Gruber, Robert and Crumrine, Debra and Elias, Peter M. and McDermott, Michael and Butler, Karina and Broderick, Annemarie and Sarig, Ofer and Sprecher, Eli and Green, Kathleen J. and McLean, W. H. Irwin and Irvine, Alan D.},
	month = nov,
	year = {2015},
	pmid = {26073755, 26073755},
	keywords = {Atopic dermatitis, Atopy, DAG, DSG1, DSP, PPK, SAM, SNP, SPINK5, Severe dermatitis, WES, Whole-exome sequencing, aCGH, atopic sensitization, desmoplakin, desmosome, eosinophilic esophagitis, mine, multiple allergies, palmoplantar keratoderma, skin barrier},
	pages = {1268--1276}
}
Downloads: 0