Page 101 - GPD-4-3

Gene & Protein in Disease ABCA12 gene in Harlequin ichthyosis

treatments, such as gene therapy and bioengineered skin Importantly, the integration of bioinformatics into
substitutes, remain largely unknown, underscoring the neonatal care protocols presents a promising future for
need for rigorous preclinical and clinical evaluation. precision medicine in HI. The prospect of implementing
Future research is needed to further elucidate the WES in newborn screening, followed by rapid in silico
full spectrum of mutations in the ABCA12 gene and analysis of pathogenic variants and affected signaling
their relationship to clinical outcomes. Collaborative pathways, could enable mutation-tailored interventions
international efforts can help to establish comprehensive during the critical neonatal period–potentially altering
genetic databases, facilitating better genotype-phenotype disease trajectory before irreversible damage occurs.
mapping and improving our understanding of the disease’s In summary, HI serves as a paradigm for how rare
molecular mechanisms. The integration of bioinformatics genetic disorders can benefit from interdisciplinary synergy
tools with advanced genomic techniques will play a among genomics, informatics, and clinical medicine.
pivotal role in these endeavors, enabling the discovery Continued investment in these areas will not only enhance
of novel therapeutic targets and strategies. In addition, our understanding of HI’s pathophysiology but also pave
advancements in patient-derived organoid models and the way for highly personalized, effective, and potentially
CRISPR-Cas9 gene-editing technologies hold promise for curative therapies. As our molecular toolkit expands, so
developing personalized treatments that directly address too does the hope for transforming HI from a devastating
the underlying genetic defects in HI. neonatal disorder into a manageable chronic condition.

7. Conclusion Acknowledgments
HI represents one of the most severe forms of congenital None.
ichthyosis, characterized by profound abnormalities in
skin barrier function due to mutations in the ABCA12 Funding
gene. These mutations disrupt lipid transport mechanisms None.
critical for normal epidermal differentiation and stratum
corneum formation, leading to the characteristic Conflict of interest
hyperkeratotic and fissured skin phenotype seen in affected The authors declare they have no competing interests.
neonates.
Over the past decade, advances in bioinformatics and Author contributions
high-throughput genomic technologies–most notably WES– Conceptualization: Dorra Guermazi, Surya Khatri, Elie
have revolutionized our understanding of HI. These tools Saliba
have not only facilitated early and accurate diagnosis, often Writing – original draft: Dorra Guermazi, Surya Khatri
within days of birth, but have also uncovered novel ABCA12 Writing – review & editing: All authors
variants, elucidated genotype–phenotype correlations,
and illuminated broader molecular pathways that are Ethics approval and consent to participate
disrupted in the disease. Functional annotation tools and Not applicable.
network-based pathway analyses are beginning to reveal the
downstream inflammatory and metabolic consequences of Consent for publication
ABCA12 dysfunction, offering new avenues for therapeutic
targeting beyond symptomatic skin care. Not applicable.
While there remains no definitive cure for HI, the Availability of data
therapeutic landscape is slowly expanding. Current Not applicable.
treatment strategies, which include systemic retinoids,
emollients, keratolytics, and infection control, have References
improved survival rates and patient outcomes. Meanwhile,
emerging approaches–such as gene therapy, lipid 1. Harlequin Ichthyosis: Medline Plus Genetics. Available from:
replacement therapy, and bioengineered skin grafts–are https://medlineplus.gov/genetics/condition/harlequin-
being explored as next-generation interventions aimed at ichthyosis [Last accessed on 2025 Jan 26].
correcting the underlying molecular defect or restoring 2. ABCA12 Gene: Medline Plus Genetics. Available from:
barrier integrity. These approaches, though experimental, https://medlineplus.gov/genetics/gene/abca12 [Last
underscore the translational potential of integrating accessed on 2025 Jan 26].
genomic data with regenerative medicine. 3. Elkhatib AM, Omar M. Ichthyosis Fetalis. In: StatPearls.

Volume 4 Issue 3 (2025) 6 doi: 10.36922/GPD025050009