Porokeratosis: An enigma beginning to unravel

Porokeratosis is a keratinization disorder with unclear etiopathogenesis, varied clinical presentation and characteristic histopathology, and is usually unresponsive to current therapeutic options. Until now, it was considered to be a clonal disorder with immunity, ultra violet radiation and other factors playing important roles in etiopathogenesis. It is now known that abnormalities in the mevalonate pathway are responsible for this clonal keratinization abnormality. New variants of porokeratosis like eruptive bullous, pruriginous, lichen planus like, follicular variants and porokeratoma have been described. While the cornoid lamella is the classical histopathologic feature, dermoscopy and reflectance confocal microscopy make the diagnosis clearer. Development of malignancy in a few variants is a concern. Linear, disseminated superficial actinic and giant lesions are most prone to developing malignancies. Bowen’s disease, squamous cell carcinoma, basal cell carcinoma and even melanoma have been reported in cases of long-standing porokeratosis. Newer modalities of therapy such as photodynamic therapy, ingenol mebutate and HMGCoA inhibitors may play a role in the future

Síndrome de Hiper IgD: espectros clínicos, achados genéticos e condutas terapêuticas / Hyper-IgD syndrome: clinical spectrum, genetic findings, and therapeutic approaches

A deficiência de mevalonato quinase (MVK; MIM #142680; ORPHA #343) é uma doença genética, espectral, rara, associadas a mutações ao longo do gene MVK causando distúrbios na síntese do colesterol, que culminam em: inflamação sistêmica com febre, adenopatia, sintomas abdominais e outros achados clínicos. Enquanto no polo leve da doença os achados mais comuns são febres recorrentes com linfadenopatia, no polo mais grave adiciona-se o acometimento do sistema nervoso central (meningites assépticas, vasculites e atraso do desenvolvimento neuropsicomotor) e do sistema hematopoiético (síndrome de ativação macrofágica). Apesar de inúmeras terapêuticas, os bloqueadores da interleucina-1 ainda são os únicos medicamentos capazes de controlar a doença e de impedir a evolução para amiloidose. Os estudos atuais visam tentar novos tratamentos, como o transplante de células-tronco hematopoiéticas, ou mesmo a terapia gênica.

Mevalonate kinase deficiency (MVK; MIM #142680; ORPHA #343) is a rare spectral genetic disorder linked to mutations along the MVK gene leading to impaired cholesterol synthesis, clinically observed as systemic inflammation with fever, adenopathy, abdominal manifestations, and other clinical findings. While on mild forms recurrent fever with lymphadenopathy is commonly observed, severe forms add to that neurological (aseptic meningitis, vasculitis, and neuropsychomotor developmental delay) and hematopoietic involvement (macrophage activation syndrome). Despite of several therapeutic approaches, blocking interleukin-1 is the only effective method to control the disease and prevent the development of systemic amyloidosis. Ongoing studies aim to test new treatments, such as hematopoietic stem cell transplantation and gene therapy.

Cloning and bioinformatics analysis of SmMK gene in Swertia mussotii / 中草药

Objective: In order to identify the function of the mevalonate kinase (MK) which is a key enzyme of the mevalonate pathway (MVA) in Swertia mussotii, and to improve the study of MVA in S. mussotii. Methods: According to the SmMK gene sequence of transcriptome of S. mussotii, the specific primers were designed, the cDNA complete sequences was obtained by RT-PCR and the sequence was analyzed using bioinformatics. Prokaryotic expression vector MBP-SmMK was constructed and transformed into Escherichia coli Rosetta (DE3) for expression. Results: The results showed that SmMK cDNA complete sequences had a length of 1 164 bp encoding 387 amino acid residues. The SmMK protein shared high identity with other MK proteins of plants. And the protein signal peptide, transmembrane region, location, secondary, and tertiary structures were analyzed and forecasted. The SDS-PAGE results showed that the expressed proteins were consistent with the anticipated size, which was 40 970. Conclusion: This work will provide a foundation for research the SmMK protein functional and study MCA in S. mussotii. At the same time, it will supply the basis to improve the production of the isoprenoids.

Skin symptoms as diagnostic clue for autoinflammatory diseases

ABSTRACT Autoinflammatory disorders are immune-mediated diseases with increased production of inflammatory cytokines and absence of detectable autoantibodies. They course with recurrent episodes of systemic inflammation and fever is the most common symptom. Cutaneous manifestations are prevalent and important to diagnosis and early treatment of the syndromes. The purpose of this review is to emphasize to dermatologists the skin symptoms present in these syndromes in order to provide their early diagnosis.

Cloning, Bioinformatic Analysis, and Prokaryotic Expression of LaMK Gene in Lepidium apetalum / 中国药学杂志

OBJECTIVE: To clone the mevalonate kinase (MK) gene involved in cardiac glycosides biosynthesis pathway of Lepidium apetalum, and carry out bioinformatic analysis, prokaryotic expression, purification, and tissue-specific expression analysis. METHODS: By analyzing the transcriptome data of L. apetalum and designing specific primers, the cDNA of LaMK gene was isolated from L. apetalum (GenBank accession No. KX290928).Escherichia coli BL21 (DE3) cells were transformed with the prokaryotic expression vector pET-32a-LaMK and used for prokaryotic expression of recombinant LaMK protein. RESULTS: The open reading frame (ORF) of LaMK was 1 137 bp, which encoded a protein of 379 amino acid residues, with a predicted molecular weight of 40.43×103. Bioinformatic analysis showed that LaMK protein may locate in cytoplasm, had no transmembrane domain and signal peptide, and exhibited specific N-terminal domain and C-terminal domain of GHMP kinase super family, as well as the binding site of ATP. Phylogenetic analysis indicated that LaMK protein had the highest homology with MK protein from cruciferous plants (such as AtMK from Arabidopsis thaliana). Through construction of the prokaryotic expression vector, the recombinant LaMK protein was successfully expressed in Escherichia coli BL21 (DE3) cells. Furthermore, the recombinant LaMK protein was purified by Ni2+ affinity chromatography. Real-time PCR analysis indicated that LaMK was expressed at a high level in flowers, low levels in leaves and roots, lower expression level in stems, and the lowest level in seedlings. CONCLUSION: In this study, the LaMK gene is cloned from L. apetalum, the prokaryotic expression system is established, and the purified recombinant LaMK protein is obtained. This study lays the foundation for preparation of the antibody of LaMK protein and research of the function of LaMK gene involved in cardiac glycosides biosynthesis pathway.

Novel Mutations causing Hyperimmunoglobulin D and Periodic Fever Syndrome.

Hyperimmunoglobulin D and periodic fever syndrome (HIDS) is a rare, hereditary autoinflammatory condition characterized by recurrent inflammatory episodes. We report a 9-year-old boy, diagnosed with HIDS due to two novel mutations, c.62C>T (p.Ala21Val) and c.372-6T>C (probable splicing defect), in the mevalonate kinase (MVK) gene. The pathogenicity of these mutations was confirmed by measurement of low MVK enzyme activity in cultured primary skin fibroblasts of the patient. The symptoms have been refractory to therapy with steroids and non steroidal anti inflammatory drugs. This report expands the genetic and ethnic spectrum of HIDS.