@article {504, title = {CARD14-associated papulosquamous eruption: A spectrum including features of psoriasis and pityriasis rubra pilaris.}, journal = {J Am Acad Dermatol}, volume = {79}, year = {2018}, month = {2018 Sep}, pages = {487-494}, abstract = {

BACKGROUND: Heterozygous mutations in caspase recruitment domain family member 14 gene (CARD14) have been shown to be associated with psoriasis and familial pityriasis rubra pilaris (PRP). Many subjects with CARD14 mutations display features of both disorders, which can result in diagnostic uncertainty. In addition, these eruptions are often recalcitrant to conventional psoriasis therapies such as methotrexate, oral retinoids, and tumor necrosis factor-α inhibitors.

OBJECTIVE: We sought to describe the clinical characteristics, family history, and response to therapy in subjects with papulosquamous eruptions due to mutations in CARD14.

METHODS: Subjects were referred for genetic testing as part of a registry of subjects with inherited disorders of keratinization. DNA was isolated from blood or saliva, and multiplex targeted sequencing or whole exome sequencing was performed. Clinical histories of subjects with CARD14 mutations were reviewed.

RESULTS: We identified 15 kindreds with CARD14-associated papulosquamous eruption (CAPE). Characteristic features of CAPE include early age of onset; prominent involvement of the cheeks, chin, and ears; family history of psoriasis or PRP; minimal response to conventional topical and systemic psoriasis therapies; and improvement with ustekinumab.

LIMITATIONS: Relatively small sample size.

CONCLUSIONS: Many subjects with CARD14 mutations display characteristics of both psoriasis and PRP. We propose the term CARD14-associated papulosquamous eruption to describe this spectrum of disease. Subjects with clinical features suggestive of CAPE should undergo CARD14 sequencing and may benefit from treatment with ustekinumab.

}, keywords = {Age of Onset, CARD Signaling Adaptor Proteins, Child, Child, Preschool, Dermatologic Agents, Facial Dermatoses, Genetic Testing, Guanylate Cyclase, Humans, Infant, Infant, Newborn, Membrane Proteins, Phenotype, Pityriasis Rubra Pilaris, Psoriasis, Retreatment, Skin Diseases, Papulosquamous, Ustekinumab}, issn = {1097-6787}, doi = {10.1016/j.jaad.2018.02.034}, author = {Craiglow, Brittany G and Boyden, Lynn M and Hu, Ronghua and Virtanen, Marie and Su, John and Rodriguez, Gabriela and McCarthy, Catherine and Luna, Paula and Larralde, Margarita and Humphrey, Stephen and Holland, Kristen E and Hogeling, Marcia and Hidalgo-Matlock, Benjamin and Ferrari, Bruno and Fernandez-Faith, Esteban and Drolet, Beth and Cordoro, Kelly M and Bowcock, Anne M and Antaya, Richard J and Ashack, Kurt and Ashack, Richard J and Lifton, Richard P and Milstone, Leonard M and Paller, Amy S 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 = {

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.

}, 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} }