Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin - 06/11/15
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>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.
El texto completo de este artículo está disponible en PDF.Key words : Atopy, skin barrier, atopic dermatitis, desmosome, desmoplakin, atopic sensitization, eosinophilic esophagitis
Abbreviations used : aCGH, AD, DSG1, DSP, PPK, SAM, SNP, SPINK5, WES
Esquema
| The Irvine group is funded by the National Children's Research Centre, Dublin, Ireland. M.A.M. is supported by the National Children's Research Centre, Dublin, Ireland. A.D.I. and W.H.I.M. are supported by the Wellcome Trust (090066/B/09/Z and 092530/Z/10/Z). The Centre for Dermatology and Genetic Medicine, University of Dundee, is supported a Wellcome Trust Strategic Award (098439/Z/12/Z to W.H.I.M.). F.J.D.S. and N.J.W. are supported by grants from the Pachyonychia Congenita Project. Work in K.J.G.'s laboratory is supported by the National Institutes of Health (R37 AR043380 and R01 AR041836) and in part by the J.L. Mayberry Endowment. P.M.E. is supported by National Institutes of Health grant R01AR061106. C. Cole is supported by the Wellcome Trust (WT strategic awards WT097945, WT092340, and WT083481). |
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| Disclosure of potential conflict of interest: M. A. McAleer has received research support from and is employed by the National Children's Research Centre. E. Pohler is employed by the University of Dundee. C. Cole has received research support from the Wellcome Trust (092530/Z/10/Z, 098439/Z/12/Z, Strategic awards 097945, 092340, and 083481), has received travel support from the University of Nottingham, and has received funding for bioinformatics user group meetings from Edinburgh Genomics. J. L. Koetsier, L. M. Godsel, R. M. Harmon, and K. J. Green have received research support from the National Institutes of Health. R. Gruber has received travel support from the Rene Touraine Foundation. W. H. I. McLean has received research support from the Wellcome Trust. A. D. Irvine has consultant arrangements with Regeneron and has received research support from the National Children's Research Centre. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 136 - N° 5
P. 1268-1276 - novembre 2015 Regresar al número
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