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American Journal of Human Genetics Jul 2020The discovery of genetic causes of inherited skin disorders has been pivotal to the understanding of epidermal differentiation, function, and renewal. Here we show via...
The discovery of genetic causes of inherited skin disorders has been pivotal to the understanding of epidermal differentiation, function, and renewal. Here we show via exome sequencing that mutations in ASPRV1 (aspartic peptidase retroviral-like 1) cause a dominant Mendelian disorder featuring palmoplantar keratoderma and lamellar ichthyosis, a phenotype that has otherwise been exclusively recessive. ASPRV1 encodes a mammalian-specific and stratified epithelia-specific protease important in processing of filaggrin, a critical component of the uppermost epidermal layer. Three different heterozygous ASPRV1 missense mutations in four unrelated ichthyosis kindreds segregate with disease and disrupt protein residues within close proximity to each other and autocatalytic cleavage sites. Expression of mutant ASPRV1 proteins demonstrates that all three mutations alter ASPRV1 auto-cleavage and filaggrin processing, a function vital to epidermal barrier integrity.
Topics: Aspartic Acid Endopeptidases; Filaggrin Proteins; Heredity; Heterozygote; Humans; Ichthyosis, Lamellar; Intermediate Filament Proteins; Mutation, Missense; Phenotype; Skin Diseases; Exome Sequencing
PubMed: 32516568
DOI: 10.1016/j.ajhg.2020.05.013 -
International Journal of Older People... Sep 2017The aims of this study were to (i) assess the effect of low-cost hygiene and emollient regimens on the skin barrier function (SBF) of people aged >65 year with xerosis...
AIMS
The aims of this study were to (i) assess the effect of low-cost hygiene and emollient regimens on the skin barrier function (SBF) of people aged >65 year with xerosis (dry skin) on their lower legs; (ii) to assess the utility of portable measures of skin barrier function in terms of stratum corneum hydration (SCH) and transepidermal water loss (TEWL) in community settings; and iii) to provide evidence for a randomised controlled trial on the treatment of adults in a resource-poor country with dry skin on their lower legs which causes and exacerbates the skin disease podoconiosis (non-filarial elephantiasis).
BACKGROUND
Age increases the risk of impaired skin barrier function which can precipitate skin breakdown. Older skin is frequently characterised by troublesome xerosis and pruritus (itching). Hygiene and emollient practices are central to maintaining skin integrity but are currently under-researched.
METHOD
A quasi-experimental pilot study of five combinations of cleansing and emollient interventions was applied to the xerotic lower legs of ten participants with no skin disease for five consecutive days. Stratum corneum hydration and transepidermal water loss were measured at baseline and day six. Products were chosen because of effectiveness, low cost and availability in a poor-resource country.
RESULTS
The greatest difference in transepidermal water loss pre-intervention-postintervention was indicated by the regimen of soapy water, 2% glycerine soak and Vaseline (mean 1.14, SD 1.27). This regimen also indicated the greatest difference in stratum corneum hydration (mean 7.92, SD 3.93). The improvement in stratum corneum hydration was significantly greater than for the control (p = .011), soap (p = .050) or water soak (p = .011).
CONCLUSION
A regimen of washing skin with soapy water, soaking in 2% glycerine for 30 min and applying Vaseline has a beneficial effect on the skin barrier function in older people. The study supports previous findings on the positive effects of glycerine on skin barrier function.
IMPLICATIONS FOR PRACTICE AND RESEARCH
Skin barrier function in older people can be improved using a regimen of washing, soaking in 2% glycerine and applying Vaseline .
Topics: Administration, Topical; Aged; Aged, 80 and over; Emollients; Female; Glycerol; Humans; Hydrogen-Ion Concentration; Ichthyosis; Leg; Petrolatum; Pilot Projects; Pruritus; Skin Care; Soaps; Treatment Outcome; Water Loss, Insensible
PubMed: 28078772
DOI: 10.1111/opn.12145 -
Indian Journal of Dermatology,... 2015
Topics: Emollients; Humans; Hyperkeratosis, Epidermolytic; Infant; Male
PubMed: 26515868
DOI: 10.4103/0378-6323.158637 -
Journal of Dermatological Science Sep 2022Sjögren-Larsson syndrome (SLS) is a neurocutaneous disorder whose causative gene is the fatty aldehyde dehydrogenase ALDH3A2 and of which ichthyosis is the major skin...
BACKGROUND
Sjögren-Larsson syndrome (SLS) is a neurocutaneous disorder whose causative gene is the fatty aldehyde dehydrogenase ALDH3A2 and of which ichthyosis is the major skin symptom. The stratum corneum contains a variety of ceramides, among which ω-O-acylceramides (acylceramides) and protein-bound ceramides are essential for skin permeability barrier formation.
OBJECTIVES
To determine the ceramide classes/species responsible for SLS pathogenesis and the enzymes that are impaired in SLS.
METHODS
Genomic DNA was collected from peripheral blood samples from an SLS patient and her parents, and whole-genome sequencing and Sanger sequencing were performed. Lipids were extracted from stratum corneum samples from the SLS patient and healthy volunteers and subjected to ceramide profiling via liquid chromatography coupled with tandem mass spectrometry.
RESULTS
A duplication (c.55_130dup) and a missense mutation (p.Lys447Glu) were found in the patient's ALDH3A2 gene. The patient had reduced levels of all acylceramide classes, with total acylceramide levels at 25 % of healthy controls. Reductions were also observed for several nonacylated ceramides: ceramides with phytosphingosine or 6-hydroxysphingosine in the long-chain base moiety were reduced to 24 % and 41 % of control levels, respectively, and ceramides with an α-hydroxy fatty acid as the fatty acid moiety were reduced to 29 %. The fatty acid moiety was shortened in many nonacylated ceramide classes.
CONCLUSION
These results suggest that reduced acylceramide levels are a primary cause of the ichthyosis symptoms of SLS, but reductions in other ceramide classes may also be involved.
Topics: Ceramides; Epidermis; Fatty Acids; Female; Humans; Ichthyosis; Ichthyosis, Lamellar; Sjogren-Larsson Syndrome
PubMed: 35973883
DOI: 10.1016/j.jdermsci.2022.08.003 -
Cell Calcium Jun 2019Ca release-activated Ca (CRAC) channels are intimately linked with health and disease. The gene encoding the CRAC channel, ORAI1, was discovered in part by genetic... (Review)
Review
Ca release-activated Ca (CRAC) channels are intimately linked with health and disease. The gene encoding the CRAC channel, ORAI1, was discovered in part by genetic analysis of patients with abolished CRAC channel function. And patients with autosomal recessive loss-of-function (LOF) mutations in ORAI1 and its activator stromal interaction molecule 1 (STIM1) that abolish CRAC channel function and store-operated Ca entry (SOCE) define essential functions of CRAC channels in health and disease. Conversely, gain-of-function (GOF) mutations in ORAI1 and STIM1 are associated with tubular aggregate myopathy (TAM) and Stormorken syndrome due to constitutive CRAC channel activation. In addition, genetically engineered animal models of ORAI and STIM function have provided important insights into the physiological and pathophysiological roles of CRAC channels in cell types and organs beyond those affected in human patients. The picture emerging from this body of work shows CRAC channels as important regulators of cell function in many tissues, and as potential drug targets for the treatment of autoimmune and inflammatory disorders.
Topics: Animals; Blood Platelet Disorders; Calcium; Calcium Release Activated Calcium Channels; Calcium Signaling; Channelopathies; Disease Models, Animal; Drug Discovery; Dyslexia; Erythrocytes, Abnormal; Humans; Ichthyosis; Migraine Disorders; Miosis; Muscle Fatigue; Mutation; Myopathies, Structural, Congenital; Neoplasm Proteins; ORAI1 Protein; Spleen; Stromal Interaction Molecule 1
PubMed: 31009822
DOI: 10.1016/j.ceca.2019.03.004 -
The British Journal of Dermatology Jun 2021Valentin 2021; :1123–1131.
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Dermatology Online Journal Jan 2021Vulvar epidermolytic hyperkeratosis is a benign entity that mimics other malignant and inflammatory vulvar dermatoses clinically and histologically requiring careful...
Vulvar epidermolytic hyperkeratosis is a benign entity that mimics other malignant and inflammatory vulvar dermatoses clinically and histologically requiring careful clinical pathologic correlation for diagnosis.
Topics: Adrenal Cortex Hormones; Aged; Calcineurin Inhibitors; Chronic Disease; Diagnosis, Differential; Female; Humans; Hyperkeratosis, Epidermolytic; Pruritus; Vulvar Diseases; Vulvar Neoplasms
PubMed: 33560797
DOI: No ID Found -
Ugeskrift For Laeger Jul 2014A new classification of inherited ichthyoses is presented based on clinical features, genetic background and pathophysiology. Ichthyoses are disorders of cornification... (Review)
Review
A new classification of inherited ichthyoses is presented based on clinical features, genetic background and pathophysiology. Ichthyoses are disorders of cornification and may be part of syndromes. Ichthyosis vulgaris, X-linked ichthyosis, autosomal recessive congenital ichthyosis and syndrome-related variants are described. Severe forms can be potentially life-threatening. Dry scaly skin can be disabling and time-consuming, as the patient needs topical therapy and sometimes also systemic retinoids. Treatment today is symptomatic, but hopefully new knowledge will lead to targeted therapies.
Topics: Dermatologic Agents; Genetic Predisposition to Disease; Humans; Ichthyosis; Skin
PubMed: 25292205
DOI: No ID Found -
Indian Pediatrics Aug 2014
Topics: Child; Humans; Ichthyosis, X-Linked; Male
PubMed: 25129014
DOI: No ID Found -
Journal of Clinical Sleep Medicine :... Jun 2021Ichthyosis, as a debilitating disease, can cause significant physical and psychological damage to children and their families, which also includes sleep impairment. We...
Ichthyosis, as a debilitating disease, can cause significant physical and psychological damage to children and their families, which also includes sleep impairment. We call attention to the importance of evaluating sleep complaints in these patients, given the scarcity of studies on this subject. As the disease commonly results in severe skin injury, it can affect social relationships and the life and sleep quality of the individuals, leading to significant psychologic damage that can persist throughout their lives.
Topics: Child; Humans; Ichthyosis; Sleep
PubMed: 33682676
DOI: 10.5664/jcsm.9208