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Gene & Protein in Disease

MINI-REVIEW
The ABCA12 gene in Harlequin ichthyosis:

Insights from bioinformatics and clinical research

Dorra Guermazi * , Surya Khatri 1 , Elias Guermazi 2 , and Elie Saliba 3,4
1
1 The Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States
of America
2 Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States
of America
3 Department of Dermatology, Warren Alpert Medical School of Brown University, Rhode Island,
United States of America
4 Department of Dermatology, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese
American University, Beirut, Lebanon

Abstract

Harlequin ichthyosis (HI) is a rare, severe, and congenital disorder that is often life-
threatening, characterized by thick, rigid skin and large, diamond-shaped plates.
These skin changes are not only aesthetically distressing but also pose significant
functional challenges for affected individuals, such as impaired thermoregulation,
restricted mobility, and heightened susceptibility to infections. The condition arises
*Corresponding author: due to mutations in the ABCA12 gene, which encodes a critical lipid transporter protein
Dorra Guermazi essential for skin barrier function. Historically, HI was nearly fatal in the neonatal
(dorra_guermazi@brown.edu)
period due to complications such as sepsis, respiratory distress, and electrolyte
Citation: Guermazi D, Khatri S, imbalances from excessive transepidermal water loss. However, advances in intensive
Guermazi E, Saliba E. The ABCA12
gene in Harlequin ichthyosis: neonatal care–including humidified incubators, prophylactic antibiotics, and early
Insights from bioinformatics and nutritional support–have improved survival rates to over 50% in recent decades.
clinical research. Gene Protein Dis. Despite these gains, lifelong morbidity persists, with survivors often facing chronic
2025;4(3):025050009.
doi: 10.36922/GPD025050009 skin inflammation, recurrent infections, and psychosocial challenges stemming
from disease visibility. This review paper explores the genetic underpinnings of HI,
Received: January 31, 2025 focusing on ABCA12 mutations and their effects on epidermal differentiation and the
Revised: June 10, 2025 formation of the skin’s stratum corneum. By utilizing advanced bioinformatics tools,
Accepted: June 16, 2025 including whole-exome sequencing, researchers are now able to identify mutations
with high precision and investigate the genotype–phenotype correlations in HI.
Published online: July 18, 2025 The review also examines the clinical challenges posed by HI, therapeutic strategies
Copyright: © 2025 Author(s). currently available, and the potential for innovative treatments such as gene therapy
This is an Open-Access article and skin-engineering. The paper aims to highlight the vital role bioinformatics plays
distributed under the terms of the
Creative Commons Attribution in understanding the molecular mechanisms of HI, facilitating earlier diagnosis and
License, permitting distribution, personalized management for affected individuals. Advances in genetic research
and reproduction in any medium, have provided new hope for improved outcomes and better quality of life for those
provided the original work is
properly cited. affected by this debilitating condition.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Harlequin ichthyosis; ABCA12 gene; Genetic mutations; Lipid transport;
regard to jurisdictional claims in
published maps and institutional Whole-exome sequencing; Gene therapy
affiliations.

Volume 4 Issue 3 (2025) 1 doi: 10.36922/GPD025050009