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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 -
Human Heredity 2023Porokeratosis is a rare chronic progressive hypokeratotic skin disease, possibly related to the mevalonate pathway. Variations in four enzymes, including...
BACKGROUND
Porokeratosis is a rare chronic progressive hypokeratotic skin disease, possibly related to the mevalonate pathway. Variations in four enzymes, including phosphomevalonate kinase (PMVK) may alter this pathway, ultimately leading to porokeratosis.
OBJECTIVES
The aim of the study was to identify the causative gene variant of porokeratosis in a Chinese family and investigate its population frequency and pathogenicity.
METHOD
In this study, Sanger sequencing was used to identify the gene variant causative of porokeratosis; its population frequency was investigated by polymerase chain reaction-restriction fragment length polymorphism in 4 patients and three normal individuals as well as in 100 normal unrelated controls; finally, the pathogenicity of the mutation and the associated structural changes were predicted.
RESULTS
We identified a novel heterozygous missense variant, c.207G>T (p. Lys69Asn) in the PMVK gene. This variant was found in all patients but not in the normal individuals in this family or in the 100 controls. In silico analysis indicated that the variant was pathogenic; p.Lys69Asn changed the length of the α-helix and the hydrogen bond pattern compared with the wild-type protein.
CONCLUSIONS
The novel variant c.207G>T (p. Lys69Asn) in the PMVK gene was the causative variant in this porokeratosis family. This finding provides further evidence for the genetic basis of this disease.
Topics: Humans; Porokeratosis; Mutation; Phosphotransferases (Phosphate Group Acceptor); Mutation, Missense; Pedigree
PubMed: 37315547
DOI: 10.1159/000531120 -
International Journal of Clinical and... 2022Porokeratosis is a disorder of keratinization with many clinical variants. The histological hallmark feature of porokeratosis is a cornoid lamella. Other accompanying...
Porokeratosis is a disorder of keratinization with many clinical variants. The histological hallmark feature of porokeratosis is a cornoid lamella. Other accompanying features include lichenoid inflammation, atrophy towards the centre of the lesion, dermal cytoid bodies, and adjacent lichenoid changes. Lichenoid keratosis is a benign cutaneous condition, thought to largely represent a degenerating seborrheic keratosis or solar lentigo. The classical histologic appearances are characterized by parakeratosis, epidermal acanthosis, and a dense band of lichenoid lymphocytic infiltrate. Since a lichenoid inflammatory reaction pattern can be seen in porokeratosis it has the potential to be misdiagnosed as a lichenoid keratosis if the cornoid lamella is not identified or missed due to sampling selection. We critically review 104 cases of benign lichenoid keratosis to establish whether any of these cases had features to support a diagnosis of porokeratosis. With 9.6% of cases considered for re-classification, we review clues to reaching this histologic diagnosis.
PubMed: 35265253
DOI: No ID Found -
Medicine Nov 2022Porokeratosis ptychotropica represents an unusual form of porokeratosis characterized by symmetrical dyskeratotic skin lesions on the gluteal clefts. Herein, we report a...
RATIONALE
Porokeratosis ptychotropica represents an unusual form of porokeratosis characterized by symmetrical dyskeratotic skin lesions on the gluteal clefts. Herein, we report a case of porokeratosis ptychotropica.
PATIENT CONCERNS
A 33-year-old man, who complained of itching papules and plaques in the gluteal cleft and the buttocks for the last 7 years. Clinical examination showed a large well-defined reddish brown verrucous plaque located on both buttocks along with satellite papules on the inner thigh. Dermoscopy and histopathological findings were consistent with porokeratosis.
DIAGNOSIS
He was diagnosed with porokeratosis ptychotropica.
OUTCOMES
No significant improvement was observed following treatment with oral acitretin and a topical retinoid.
LESSONS
The case report highlights the need for awareness amongst dermatologists for porokeratosis ptychotropica as a differential diagnosis for pruritic papules in the gluteal fold.
Topics: Male; Humans; Adult; Porokeratosis; Buttocks; Thigh; Acitretin; Pruritus; Plaque, Amyloid
PubMed: 36451470
DOI: 10.1097/MD.0000000000032074 -
Cureus Jul 2022Linear porokeratosis is a cutaneous disorder that typically presents in a unilateral linear formation. While the exact cause of linear porokeratosis is unknown, it is...
Linear porokeratosis is a cutaneous disorder that typically presents in a unilateral linear formation. While the exact cause of linear porokeratosis is unknown, it is thought to be a downstream effect of disrupted cholesterol synthesis and mevalonate accumulation. Our patient is a 61-year-old male with an unusual case presentation of bilateral linear porokeratosis. He had failed numerous standard therapies. Pathologic examination of a skin biopsy was consistent with bilateral linear porokeratosis. Through a PubMed search, there have been limited reported cases of unilateral linear porokeratosis, but there have not been any reported cases of bilateral linear porokeratosis. There are currently limited therapies with satisfactory outcomes for variants of porokeratosis. While there are some studies on the topical application of cholesterol/lovastatin, limited studies have been performed on the linear form. Our study evaluates the efficacy of compounded topical cholesterol 2%/lovastatin 2% ointment on bilateral linear porokeratosis. The patient demonstrated a significant reduction of porokeratotic lesions on the treated arm compared to the untreated arm. Cholesterol/lovastatin is alternative therapy that can be considered in the treatment of linear porokeratosis and other porokeratosis variants.
PubMed: 36060323
DOI: 10.7759/cureus.27540 -
Journal of Family Medicine and Primary... Mar 2022Porokeratosis is a keratinization disorder characterized by hyperkeratotic sharply demarcated plaques with central atrophy and histopathologically, by cornoid lamella. A...
Porokeratosis is a keratinization disorder characterized by hyperkeratotic sharply demarcated plaques with central atrophy and histopathologically, by cornoid lamella. A 30-year-old male presented with multiple pruritic dark raised skin lesions over the trunk, face, and upper limbs for past 3 years. Cutaneous examination revealed hyperkeratotic annular plaques with raised margins over face, trunk, and arms. Histopathology revealed marked hyperkeratosis with irregular acanthosis and papillomatosis. Vertical parakeratotic foci and focal hypergranulosis were seen. Hence, a diagnosis of disseminated superficial porokeratosis was made. We present this rare case which may have association with systemic disease, immunosuppression, and malignant transformation.
PubMed: 35495808
DOI: 10.4103/jfmpc.jfmpc_1232_21 -
Nagoya Journal of Medical Science Feb 2024Whole-exome and whole-genome sequencing have become widespread in approximately the last 15 years, and the predisposing factors and pathomechanisms of inflammatory... (Review)
Review
Whole-exome and whole-genome sequencing have become widespread in approximately the last 15 years, and the predisposing factors and pathomechanisms of inflammatory keratinization diseases, which have been unknown for a long time, have gradually been revealed. Hence, various inflammatory keratinization diseases are recognized to cause innate immunity hyperactivation. Therefore, we have been advocating for the clinical entity, "autoinflammatory keratinization diseases (AiKDs)" since 2017. AiKDs are inflammatory keratinization diseases caused by autoinflammatory-related pathomechanisms in the skin. The aberrant activation of innate immunity and the resultant autoinflammation in the epidermis and the superficial dermis in AiKDs cause hyperkeratosis in the epidermis. Our initially proposed concept of AiKDs included generalized pustular psoriasis and related conditions, pityriasis rubra pilaris type V, and familial keratosis lichenoides chronica. Since then, the number of diseases known to be AiKDs has increased as previously unknown disease-causing factors and pathogenetic mechanisms of inflammatory keratinization diseases have been clarified one by one. To date, porokeratosis, hidradenitis suppurative, keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome, and AiKDs associated with epidermal growth factor receptor (EGFR) deficiency or with hepatitis and autism have been recognized as AiKDs. The concept of AiKDs is considered extremely useful in our precise understanding of the pathogeneses behind inflammatory keratinization diseases and our appropriate treatment method selection. The number of AiKDs is expected to grow with the clarification of the pathomechanisms of further inflammatory keratinization diseases.
Topics: Humans; Keratosis; Skin; Skin Neoplasms; Syndrome
PubMed: 38505726
DOI: 10.18999/nagjms.86.1.1 -
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 -
Biochimica Et Biophysica Acta.... Dec 2020Vesicular nucleotide transporter (VNUT) is the last identified member of the SLC17 organic anion transporter family, which plays a central role in vesicular storage in... (Review)
Review
Vesicular nucleotide transporter (VNUT) is the last identified member of the SLC17 organic anion transporter family, which plays a central role in vesicular storage in ATP-secreting cells. The discovery of VNUT demonstrated that, despite having been neglected for a long time, vesicular ATP release represents a major pathway for purinergic chemical transmission, which had been mainly attributed to ATP permeation channels. This article summarizes recent advances in our understanding of the mechanism of VNUT and its physiopathological roles as well as the development of inhibitors. Regulating the activity and/or the expression of VNUT represents a new and promising therapeutic strategy for the treatment of multiple diseases.
Topics: Adenosine Triphosphate; Animals; Circadian Rhythm; Clodronic Acid; Humans; Inflammation; Neurons; Nucleotide Transport Proteins; Pain Perception; Porokeratosis
PubMed: 32652056
DOI: 10.1016/j.bbamem.2020.183408 -
Skin Appendage Disorders Nov 2021The lesions of porokeratosis (PK) lead to skin atrophy and scarring as long as they spread centrifugally. PK affecting the nail unit is seldom described.
BACKGROUND
The lesions of porokeratosis (PK) lead to skin atrophy and scarring as long as they spread centrifugally. PK affecting the nail unit is seldom described.
OBJECTIVE
The aim was to revise the previously reported cases of ungual PK and to present 3 new cases.
METHODS
A PubMed search was performed with the keywords "nail" and "porokeratosis." Previously reported cases as well as 3 new cases are depicted in tables.
RESULTS
Only 11 cases of ungual PK were found; 3 new cases have been added. All patients presented with typical lesions of PK (Mibelli, isolated, segmental, or ostial eccrine types) that happened to affect nails due to nail matrix or nail bed compromise, resulting in mild to severe nail scarring, including irreversible anonychia. The present 3 case series contrast with the previous single case reports.
CONCLUSIONS
PK affecting the nails is exceedingly rare. Changes in nails affected by PK are irreversible, since, as on the skin, this is a chronic scarring process.
PubMed: 34901183
DOI: 10.1159/000516304