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Acta Dermato-venereologica Jul 2021
Topics: Eccrine Glands; Extremities; Humans; Keratosis; Nevus; Porokeratosis; Skin Neoplasms
PubMed: 34159394
DOI: 10.2340/00015555-3851 -
Biological Research May 2021The MVD gene mutations are identified in porokeratosis, which is considered a skin-specific autoinflammatory keratinization disease. However, the biological function of...
BACKGROUND
The MVD gene mutations are identified in porokeratosis, which is considered a skin-specific autoinflammatory keratinization disease. However, the biological function of MVD gene remains largely unknown. Therefore, we analyzed the function of mvda gene, orthologous to the human MVD gene, in developing zebrafish.
METHODS
Morpholino antisense oligonucleotide technique was used to generate mvda loss-of-function phenotypes. Knockdown of mvda was confirmed by RT-PCR and Sanger sequencing. Scanning and transmission electron microscopy were performed to analyze the morphology of the epidermis. Angiogenesis study was presented using the Tg(fli1a:EGFP) transgenic strain. In addition, acridine orange staining was used to examine the apoptotic cells in vivo.
RESULTS
As expected, the mvda morphants showed abnormal morphology of the epidermis. Moreover, we observed ectopic sprouts in trunk angiogenesis and impaired formation of the caudal vein plexus in the mvda-deficient zebrafish. Besides, increased apoptosis was found throughout the tail, heart, and eyes in mvda zebrafish morphants.
CONCLUSIONS
These findings indicated the essential role of mvda in the early development of zebrafish. This was the first in vivo knockdown study of the zebrafish mvda gene, which might offer insight into the biological function of the human MVD gene.
Topics: Animals; Animals, Genetically Modified; Cell Differentiation; Humans; Morphogenesis; Phenotype; Zebrafish
PubMed: 34051853
DOI: 10.1186/s40659-021-00341-7 -
The Australasian Journal of Dermatology Aug 2021
Topics: Aged, 80 and over; Carcinoma, Squamous Cell; Humans; Leg; Male; Porokeratosis; Radiotherapy, Intensity-Modulated
PubMed: 33954983
DOI: 10.1111/ajd.13605 -
Actas Dermo-sifiliograficas Apr 2021
PubMed: 33939988
DOI: 10.1016/j.ad.2019.12.011 -
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 -
Acta Dermato-venereologica Apr 2021
Topics: Child; Female; Humans; Porokeratosis; Skin Abnormalities
PubMed: 33734419
DOI: 10.2340/00015555-3789 -
Cureus Feb 2021Background Porokeratosis (PK) is a rare group of keratinization disorders. While the overall prognosis of PK is favorable, malignant transformation of PK to skin cancer...
Background Porokeratosis (PK) is a rare group of keratinization disorders. While the overall prognosis of PK is favorable, malignant transformation of PK to skin cancer has been reported in 6.9% to 11.6% of the cases. Prior estimates of malignant transformation of PK have been based on reviews of published cases, which introduces possible publication bias. We aim to eliminate this potential bias and quantify the characteristics, risk factors, and malignancy potential of PK. Methodology A single-center retrospective chart review of patients with a diagnosis of PK was conducted. Results In this study, 6.4% to 16.4% of histologically confirmed PK lesions demonstrated malignant transformation. A higher proportion of disseminated superficial actinic porokeratosis (DSAP) cases (as high as 29.3%) showed malignant transformation compared to PK of Mibelli (as high as 6.0%). Out of the two cases of linear PK, both demonstrated malignant transformation. Conclusions In summary, PKs are at risk for malignant transformation, and patients with DSAP and linear PK, in particular, should receive more long-term surveillance. Limitations of this study include the inability to control for confounding factors due to the retrospective nature and the small size of our cohort.
PubMed: 33680623
DOI: 10.7759/cureus.13083 -
JAAD Case Reports Mar 2021
PubMed: 33644282
DOI: 10.1016/j.jdcr.2021.01.012 -
Acta Dermato-venereologica Mar 2021
Topics: Carboxy-Lyases; Humans; Mutation; Pemphigoid, Bullous; Porokeratosis
PubMed: 33554266
DOI: 10.2340/00015555-3764 -
Acta Dermato-venereologica Feb 2021Porokeratoses are a heterogeneous group of keratinization disorders. For linear porokeratosis and disseminated superficial actinic porokeratosis, a heterozygous...
Porokeratoses are a heterogeneous group of keratinization disorders. For linear porokeratosis and disseminated superficial actinic porokeratosis, a heterozygous pathogenic germline variant in a mevalonate pathway gene and a postzygotic second hit mutation present in affected skin have been shown to be the patho-genetic mechanism for the development of the lesions. However, the molecular mechanism leading to development of porokeratosis plantaris, palmaris et disseminata is not known. This study analysed a cohort of 4 patients with linear porokeratosis and 3 patients with porokeratosis plantaris, palmaris et disseminata, and performed mutation analyses of DNA extracted from blood samples and skin biopsies. All of the study patients carried the heterozygous germline variant c.70+5G>A in the MVD gene. Loss of heterozygosity due to a second hit mutation was found in affected skin of 3 patients with linear porokeratosis and 2 patients with porokeratosis plantaris, palmaris et disseminata. These results suggest that porokeratosis plantaris, palmaris et disseminata shares the same pathogenetic mechanism as other porokeratosis subtypes and belongs to the phenotypic spectrum of MVD-associated porokeratosis.
Topics: DNA Mutational Analysis; Genitalia; Humans; Mutation; Porokeratosis; Skin
PubMed: 33491095
DOI: 10.2340/00015555-3753