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Indian Journal of Dermatology,... 2016
Topics: Adult; Facial Dermatoses; Female; Humans; Male; Porokeratosis; Sunlight; Young Adult
PubMed: 27088949
DOI: 10.4103/0378-6323.174391 -
Journal of Clinical Medicine Apr 2021Mevalonate kinase-associated diseases (MKAD) are caused by pathogenic mutations in the mevalonate kinase gene () and encompass several phenotypically different rare and...
Mevalonate kinase-associated diseases (MKAD) are caused by pathogenic mutations in the mevalonate kinase gene () and encompass several phenotypically different rare and hereditary autoinflammatory conditions. The most serious is a recessive systemic metabolic disease called mevalonic aciduria, and the most recently recognized is disseminated superficial actinic porokeratosis, a dominant disease limited to the skin. To evaluate a possible correlation between genotypes and (1) the different MKAD clinical subtypes or (2) the occurrence of severe manifestations, data were reviewed for all patients with variants described in the literature (N = 346), as well as those referred to our center (N = 51). The genotypes including p.(Val377Ile) (homozygous or compound heterozygous) were more frequent in mild systemic forms but were also sometimes encountered with severe disease. We confirmed that amyloidosis was more prevalent in patients compound heterozygous for p.(Ile268Thr) and p.(Val377Ile) than in others and revealed new associations. Patients homozygous for p.(Leu264Phe), p.(Ala334Thr) or compound heterozygous for p.(His20Pro) and p.(Ala334Thr) had increased risk of severe neurological or ocular symptoms. All patients homozygous for p.(Leu264Phe) had a cataract. The variants associated with porokeratosis were relatively specific and more frequently caused a frameshift than in patients with other clinical forms (26% vs. 6%). We provide practical recommendations focusing on phenotype-genotype correlation in MKAD that could be helpful for prophylactic management.
PubMed: 33917151
DOI: 10.3390/jcm10081552 -
Metabolites Nov 2023Porokeratosis is a heterogeneous group of keratinising disorders characterised by the presence of particular microscopic structural changes, namely the presence of the... (Review)
Review
Porokeratosis is a heterogeneous group of keratinising disorders characterised by the presence of particular microscopic structural changes, namely the presence of the cornoid lamella. This structure develops as a consequence of a defective isoprenoid pathway, critical for cholesterol synthesis. Commonly recognised variants include disseminated superficial actinic porokeratosis, disseminated superficial porokeratosis, porokeratosis of Mibelli, palmoplantar porokeratosis (including porokeratosis palmaris et plantaris disseminata and punctate porokeratosis), linear porokeratosis, verrucous porokeratosis (also known as genitogluteal porokeratosis), follicular porokeratosis and porokeratoma. Apart from the clinical presentation and epidemiology of each variant listed, this review aims at providing up-to-date information on the precise genetic background, introduces imaging methods facilitating the diagnosis (conventional and ultraviolet-induced fluorescence dermatoscopy, reflectance confocal microscopy and pathology), discusses their oncogenic potential and reviews the literature data on the efficacy of the treatment used, including the drugs directly targeting the isoprenoid-mevalonate pathway.
PubMed: 38132857
DOI: 10.3390/metabo13121176 -
JAMA Dermatology May 2019Linear porokeratosis features linear and whorled configurations of keratotic papules and plaques, with coronoid lamellae present on histologic examination. Because...
IMPORTANCE
Linear porokeratosis features linear and whorled configurations of keratotic papules and plaques, with coronoid lamellae present on histologic examination. Because linear porokeratosis manifests in the lines of Blaschko representing the dorsoventral migration patterns of keratinocyte precursors, it has been suggested that postzygotic somatic mutation underlies the disease. However, no genetic evidence has supported this hypothesis to date.
OBJECTIVE
To identify genetic mutations associated with linear porokeratosis.
DESIGN, SETTING, AND PARTICIPANTS
Paired whole-exome sequencing of affected skin and blood/saliva samples from 3 participants from 3 academic medical centers with clinical and histologic diagnoses of linear porokeratosis.
INTERVENTIONS OR EXPOSURES
Whole-exome sequencing of paired blood/saliva and affected tissue samples isolated from linear porokeratosis lesions.
MAIN OUTCOMES AND MEASURES
Germline and somatic genomic characteristics of participants with linear porokeratosis.
RESULTS
Of the 3 participants, 2 were male. Participant ages ranged from 5 to 20 years old. We found a combination of a novel germline mutation and a novel somatic mutation within affected tissue in all cases. One participant had a germline heterozygous PMVK c.329G>A mutation and a somatic copy-neutral loss of heterozygosity confined to the lesional skin, while a second had a germline heterozygous PMVK c.79G>T mutation and an additional PMVK c.379C>T mutation in the lesional skin. In a third participant, there was a germline splice-site mutation in MVD (c.70 + 5G>A) and a somatic deletion in MVD causing frameshift and premature codon termination within the lesional skin (c.811_815del, p.F271Afs*33 frameshift).
CONCLUSIONS AND RELEVANCE
Our findings suggest that linear porokeratosis is associated with the presence of second-hit postzygotic mutations in the genes that encode enzymes within the mevalonate biosynthesis pathway, and provide further evidence that the mevalonate pathway may be a potential target for therapeutic intervention in porokeratosis.
Topics: Academic Medical Centers; Child, Preschool; DNA Copy Number Variations; DNA Mutational Analysis; Germ-Line Mutation; Humans; Male; Phosphotransferases (Phosphate Group Acceptor); Porokeratosis; Sampling Studies; Sensitivity and Specificity; Exome Sequencing; Young Adult
PubMed: 30942823
DOI: 10.1001/jamadermatol.2019.0016 -
Acta Dermato-venereologica Aug 2023This retrospective registry-based cohort study aimed to estimate the incidence and prevalence of genodermatoses in the Swedish population and to analyse associated...
This retrospective registry-based cohort study aimed to estimate the incidence and prevalence of genodermatoses in the Swedish population and to analyse associated healthcare usage. Patients diagnosed with genodermatoses were identified from the patient registry of Sahlgrenska University Hospital (Gothenburg, Sweden) between 2016 and 2020. Clinical data from medical records were used to verify diagnoses recorded in the National Patient Registry (NPR). The NPR was then searched for International Classification of Diseases, Tenth Revision (ICD-10) codes Q80-82 and Q84 from 2001 to 2020. The local cohort included 298 patients with 36 unique genodermatosis diagnoses. Verification of these diagnoses in the NPR showed positive predictive values of over 90%. The NPR search yielded 13,318 patients with 73 unique diagnoses, including ichthyoses (n = 3,341; 25%), porokeratosis (n = 2,277; 17%), palmoplantar keratodermas (n = 1,754; 13%), the epidermolysis bullosa group (n = 1011; 7%); Darier disease (n = 770; 6%), Hailey-Hailey disease (n = 477; 4%) and Gorlin syndrome (n = 402; 3%). The incidence and prevalence of each diagnosis were calculated based on the nationwide cohort and are reported. A total of 149,538 outpatient visits were registered, a mean of 4.6 visits per patient. This study provides a valuable resource for the epidemiology of genodermatoses by reporting on the incidence and prevalence of 73 different genodermatoses.
Topics: Humans; Incidence; Prevalence; Sweden; Cohort Studies; Retrospective Studies
PubMed: 37615526
DOI: 10.2340/actadv.v103.12404 -
Dermatopathology (Basel, Switzerland) May 2023Spiny keratoderma (SK) was first described by Brown in 1871 and is characterized by numerous 1-2 mm spines of keratin on the palms and soles, usually sparing the dorsal...
Spiny keratoderma (SK) was first described by Brown in 1871 and is characterized by numerous 1-2 mm spines of keratin on the palms and soles, usually sparing the dorsal surfaces, or disseminated over the trunk. Histologically, the "spine" represents a column of hyperkeratosis. Several different forms are known, including familial, sporadic, post-inflammatory and paraneoplastic. Although an association of SK with melanoma has been reported, the significance of such co-occurrence remains unclear due to the limited number of cases. To increase the body of knowledge and shed further light on this rare condition, we present a case of SK in a patient with a recent history of melanoma in situ.
PubMed: 37218903
DOI: 10.3390/dermatopathology10020021 -
Indian Journal of Dermatology,... 2023
Topics: Humans; Porokeratosis; Buttocks; Biopsy
PubMed: 34245530
DOI: 10.25259/IJDVL_122_2021 -
Dermatology Online Journal Mar 2019Epidermodysplasia verruciformis (EV) is an autosomal recessive genodermatosis characterized by susceptibility to beta-genus human papillomavirus (HPV) infection. Owing...
Epidermodysplasia verruciformis (EV) is an autosomal recessive genodermatosis characterized by susceptibility to beta-genus human papillomavirus (HPV) infection. Owing to TMC6/EVER1 and TMC8/EVER2 mutations that lead to abnormal transmembrane channels in the endoplasmic reticulum involved in immunological pathways, keratinocytes cannot combat infection from non-pathogenic HPV strains. Mutations involving RHOH, MST-1, CORO1A, and IL-7 have also been associated with EV in patients without TMC6 or TMC8 mutations. We highlight a 27-year-old man with multiple violaceous flat-topped papules with scale and irregular borders distributed on his chest, extremities, abdomen, and back. The striking physical examination and the subsequent biopsy findings of enlarged nests of cells in the granular and spinous layers with blue-gray cytoplasm and keratohyaline granules confirmed the diagnosis. We conclude with a brief discussion on the differential diagnosis, which includes confluent and reticulated papillomatosis, Darier disease, and disseminated superficial actinic porokeratosis.
Topics: Adult; Darier Disease; Diagnosis, Differential; Epidermodysplasia Verruciformis; Humans; Male; Membrane Proteins; Papilloma; Papillomavirus Infections; Porokeratosis
PubMed: 30982308
DOI: No ID Found -
JAAD Case Reports Nov 2022
PubMed: 36186413
DOI: 10.1016/j.jdcr.2022.08.044 -
SAGE Open Medical Case Reports 2022Genitogluteal porokeratosis is a rare localized disorder of keratinization. Due to the rarity of the case and non-specific keratotic lesion, it is often misdiagnosed...
Genitogluteal porokeratosis is a rare localized disorder of keratinization. Due to the rarity of the case and non-specific keratotic lesion, it is often misdiagnosed until a histological examination is performed. Treatment of this condition can be challenging, which comprises various topical and systemic drugs, lasers, cryotherapy, phototherapy, and also surgical intervention. Regular follow-up is necessary in the view of this disorder being a premalignant condition.
PubMed: 36467011
DOI: 10.1177/2050313X221139559