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Indian Dermatology Online Journal 2023
PubMed: 37521240
DOI: 10.4103/idoj.idoj_408_22 -
Genes & Diseases Jul 2022Mevalonate kinase (MK)-associated diseases encompass a broad spectrum of rare auto-inflammatory conditions, all resulting from pathogenic variants in the mevalonate... (Review)
Review
Mevalonate kinase (MK)-associated diseases encompass a broad spectrum of rare auto-inflammatory conditions, all resulting from pathogenic variants in the mevalonate kinase gene (). Their clinical manifestations are highly variable, ranging from more or less serious systemic disorders, such as hereditary recurrent fevers, to purely localized pathologies such as porokeratosis. The oldest condition identified as linked to this gene is a metabolic disease called mevalonic aciduria, and the most recent is disseminated superficial actinic porokeratosis, a disease limited to the skin. The modes of inheritance of MK-associated diseases also diverge among the different subtypes: recessive for the systemic subtypes and dominant with a post-zygotic somatic genetic alteration for -associated porokeratosis. This review quickly retraces the historical steps that led to the description of the various MK-associated disease phenotypes and to a better understanding of their pathophysiology, then summarizes and compares the different genetic mechanisms involved in this group of disorders, and finally discusses the diverse causes that could underlie this phenotypic heterogeneity.
PubMed: 35685471
DOI: 10.1016/j.gendis.2021.05.002 -
Annales de Dermatologie Et de... Sep 2022
Topics: Humans; Porokeratosis
PubMed: 35305816
DOI: 10.1016/j.annder.2022.02.002 -
Journal of Clinical Rheumatology :... Dec 2021
Topics: Abatacept; Humans; Porokeratosis
PubMed: 33337807
DOI: 10.1097/RHU.0000000000001691 -
Human Mutation Aug 2021CDAGS Syndrome is a rare congenital disorder characterized by Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and...
CDAGS Syndrome is a rare congenital disorder characterized by Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations. We performed whole exome and Sanger sequencing to identify the underlying molecular cause in five patients with CDAGS syndrome from four distinct families. Whole exome sequencing revealed biallelic rare variants that disrupt highly conserved nucleotides within the RNU12 gene. RNU12 encodes a small nuclear RNA that is a component of the minor spliceosome and is essential for minor intron splicing. Targeted sequencing confirmed allele segregation within the four families. All five patients shared the same rare mutation NC_000022.10:g.43011402C>T, which alters a highly conserved nucleotide within the precursor U12 snRNA 3' extension. Each of them also carried a rare variant on the other allele that either disrupts the secondary structure or the Sm binding site of the RNU12 snRNA. Whole transcriptome sequencing analysis of lymphoblastoid cells identified 120 differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events in the patient. These findings provide evidence of the involvement of RNU12 in craniosynostosis, anal and genitourinary patterning, and cutaneous disease.
Topics: Anal Canal; Craniosynostoses; Digestive System Abnormalities; Humans; Porokeratosis; RNA Splicing; RNA, Small Nuclear
PubMed: 34085356
DOI: 10.1002/humu.24239 -
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 -
Postepy Dermatologii I Alergologii Feb 2021
PubMed: 34408586
DOI: 10.5114/ada.2021.104293 -
Seminars in Diagnostic Pathology Jan 2024The unenlightened clinician may submit a skin specimen to the lab and expect an "answer." The experienced clinician knows that in performing skin biopsies, it is... (Review)
Review
The unenlightened clinician may submit a skin specimen to the lab and expect an "answer." The experienced clinician knows that in performing skin biopsies, it is critical to select the most appropriate: 1) anatomic location for the biopsy; 2) type of biopsy; 3) depth and breadth of the biopsy; and 4) medium for hematoxylin and eosin staining (formalin) or direct immunofluorescence (Michel's Transport Medium or normal saline). Demographic information, anatomic location, clinical context, and differential diagnosis are all critical components of a properly completed requisition form. Proper biopsy design and appropriate grossing of the tissue at the bedside should be added to this list. In this article, we review the basics of gross pathologic examination and then provide four examples to demonstrate that optimal clinical-pathologic correlation requires the clinician consider the needs of the pathologist when tissue is presented to the lab.
PubMed: 38336505
DOI: 10.1053/j.semdp.2024.01.007 -
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 -
Journal of Cutaneous Pathology Dec 2022
Topics: Humans; Porokeratosis
PubMed: 35075675
DOI: 10.1111/cup.14195