@article {921,
	title = {Mutations in ASPRV1 Cause Dominantly Inherited Ichthyosis.},
	journal = {Am J Hum Genet},
	volume = {107},
	year = {2020},
	month = {2020 07 02},
	pages = {158-163},
	abstract = {<p>The discovery of genetic causes of inherited skin disorders has been pivotal to the understanding of epidermal differentiation, function, and renewal. Here we show via exome sequencing that mutations in ASPRV1 (aspartic peptidase retroviral-like 1) cause a dominant Mendelian disorder featuring palmoplantar keratoderma and lamellar ichthyosis, a phenotype that has otherwise been exclusively recessive. ASPRV1 encodes a mammalian-specific and stratified epithelia-specific protease important in processing of filaggrin, a critical component of the uppermost epidermal layer. Three different heterozygous ASPRV1 missense mutations in four unrelated ichthyosis kindreds segregate with disease and disrupt protein residues within close proximity to each other and autocatalytic cleavage sites. Expression of mutant ASPRV1 proteins demonstrates that all three mutations alter ASPRV1 auto-cleavage and filaggrin processing, a function vital to epidermal barrier integrity.</p>},
	keywords = {Aspartic Acid Endopeptidases, Heredity, Heterozygote, Humans, Ichthyosis, Lamellar, Intermediate Filament Proteins, Mutation, Missense, Phenotype, Skin Diseases, Whole Exome Sequencing},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2020.05.013},
	author = {Boyden, Lynn M and Zhou, Jing and Hu, Ronghua and Zaki, Theodore and Loring, Erin and Scott, Jared and Traupe, Heiko and Paller, Amy S and Lifton, Richard P and Choate, Keith A}
}
@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}
}
