@article {114,
	title = {Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome.},
	journal = {Hum Mol Genet},
	volume = {25},
	year = {2016},
	month = {2016 Jan 15},
	pages = {348-57},
	abstract = {<p>Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin. </p>},
	keywords = {Amino Acid Sequence, Cardiomyopathies, Child, Child, Preschool, Connexin 43, Desmoplakins, Desmosomes, Female, Humans, Infant, Male, Molecular Sequence Data, Mutation, Missense, Myocardium, Protein Transport, Sequence Alignment, Skin, Skin Diseases, Genetic, Syndrome},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddv481},
	author = {Boyden, Lynn M and Kam, Chen Y and Hern{\'a}ndez-Mart{\'\i}n, Angela and Zhou, Jing and Craiglow, Brittany G and Sidbury, Robert and Mathes, Erin F and Maguiness, Sheilagh M and Crumrine, Debra A and Williams, Mary L and Hu, Ronghua and Lifton, Richard P and Elias, Peter M and Green, Kathleen J and Choate, Keith A}
}
@article {187,
	title = {Frequent somatic reversion of KRT1 mutations in ichthyosis with confetti.},
	journal = {J Clin Invest},
	volume = {125},
	year = {2015},
	month = {2015 Apr},
	pages = {1703-7},
	abstract = {<p>Widespread reversion of genetic disease is rare; however, such events are particularly evident in some skin disorders in which normal clones develop on a background of affected skin. We previously demonstrated that mutations in keratin 10 (KRT10) cause ichthyosis with confetti (IWC), a severe dominant disorder that is characterized by progressive development of hundreds of normal skin spots via revertant mosaicism. Here, we report on a clinical and histological IWC subtype in which affected subjects have red, scaly skin at birth, experience worsening palmoplantar keratoderma in childhood, and develop hundreds of normal skin spots, beginning at around 20 years of age, that increase in size and number over time. We identified a causal de novo mutation in keratin 1 (KRT1). Similar to IWC-causing KRT10 mutations, this mutation in KRT1 resulted in a C-terminal frameshift, replacing 22 C-terminal amino acids with an alternate 30-residue peptide. Mutant KRT1 caused partial collapse of the cytoplasmic intermediate filament network and mislocalized to the nucleus. As with KRT10 mutations causing IWC, reversion of KRT1 mutations occurred via mitotic recombination. Because reversion is not observed with other disease-causing keratin mutations, the results of this study implicate KRT1 and KRT10 C-terminal frameshift mutations in the high frequency of revertant mosaicism in IWC. </p>},
	keywords = {Adult, Age of Onset, Amino Acid Sequence, Cell Line, Tumor, Cell Nucleus, Child, Child, Preschool, Chromosomes, Human, Pair 12, Cytoskeleton, Frameshift Mutation, Humans, Ichthyosis, Intermediate Filaments, Keratin-1, Keratinocytes, Loss of Heterozygosity, Male, Molecular Sequence Data, Mosaicism, Phenotype, Polymorphism, Single Nucleotide, Protein Transport, Transfection},
	issn = {1558-8238},
	doi = {10.1172/JCI64415},
	author = {Choate, Keith A and Lu, Yin and Zhou, Jing and Elias, Peter M and Zaidi, Samir and Paller, Amy S and Farhi, Anita and Nelson-Williams, Carol and Crumrine, Debra and Milstone, Leonard M and Lifton, Richard P}
}
