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Source publication
Autosomal recessive congenital ichthyoses (ARCI) are a skin pathology due to genetic causes characterized by a variable degree of desquamation, accompanied by erythema. The degree of symptoms is variable, different altered genes are involved, and the symptoms drastically affect patients’ quality of life. Topical treatments are a first-choice strate...
Citations
... Autosomal recessive congenital ichthyosis (ARCI) represents a genetically diverse collection of disorders marked by aberrant keratinization of the skin, which contributes to substantial morbidity and diminished quality of life (1). Within the spectrum of ARCI, mutations in the ABCA12 gene are notably associated with more severe phenotypes, including harlequin ichthyosis and congenital ichthyosiform erythroderma (2). The prevalence of Autosomal Recessive Congenital Ichthyosis (ARCI) is estimated to range from approximately 1 in 138,000 to 1 in 300,000 live births, with significant variations in incidence observed across different populations, likely attributable to factors such as founder effects (3). ...
Background
Autosomal recessive congenital ichthyosis (ARCI) is a group of genetic skin disorders characterized by abnormal keratinization, leading to significant health issues and reduced quality of life. ARCI encompasses harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). While all ARCI genes are linked to LI and CIE, HI is specifically associated with severe mutations in the ABCA12 gene. Milder forms like LI and CIE usually involve at least one non-truncating ABCA12 variant.
Methods
Whole-exome sequencing (WES) was performed on fetal and parental DNA, and ABCA12 gene variants were validated by Sanger sequencing. The functional effect of the novel variant c.7104 + 6T > A was evaluated using an in vitro minigene system, with splicing analysis conducted via PCR and Sanger sequencing.
Results
A compound heterozygous variation in the ABCA12 gene, comprising c.5784G > A (p.W1928*) and c.7104 + 6T > A, was identified in the fetus, inherited from the father and mother, respectively. According to ACMG guidelines, the c.7104 + 6T > A variant is classified as a Variant of Uncertain Significance (VUS). Computational predictions suggested that this variant affects splicing. A minigene assay further confirmed that the c.7104 + 6T > A variant in ABCA12 leads to two types of aberrant mRNA splicing: a 69-base pair deletion (c.7036_7104del, p.Val2346_Glu2368del) and skipping of Exon 47, both of which result in a premature stop codon and a truncated protein.
Conclusion
In conclusion, this study identified a novel genetic variant, c.7104 + 6T > A in ABCA12, as the cause of ARCI in a fetus, thereby enriched the known ABCA12 mutation spectrum.
Purpose
Pruritus is an unpleasant sensation that creates the urge to scratch. In many chronic conditions, relentless pruritus and scratching perpetuates a vicious itch-scratch cycle. Uncontrolled itch can detrimentally affect quality of life and may lead to sleep disturbance, impaired concentration, financial burden, and psychological suffering. Recent strides have been made to develop guidelines and investigate new therapies to treat some of the most common severely pruritic conditions, however, a large group of diseases remains underrecognized and undertreated. The purpose of this article is to provide a comprehensive review of the challenges hindering the treatment of pruritus.
Methods
An online search was performed using PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov from 1994 to 2024. Included studies were summarized and assessed for quality and relevance in treating pruritus.
Results
Several barriers to treating pruritus emerged, including variable presentation, objective measurement of itch, and identifying therapeutic targets. Itch associated with autoimmune conditions, connective tissue diseases, genodermatoses, cutaneous T-cell lymphoma, and pruritus of unknown origin were among the etiologies with the greatest unmet needs.
Conclusion
Treating pruritus poses many challenges and there are many itchy conditions that have no yet been addressed. There is an urgent need for large-scale controlled studies to investigate potential targets for these conditions and novel therapies.
