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Gene & Protein in Disease ABCA12 gene in Harlequin ichthyosis

Table 1. Summary of the contributions of bioinformatics and refine genotype–phenotype maps, guiding prognostic
sequencing technologies to the study and management of HI stratification. 4,9
Approach/ Function Benefits Challenges/ 3.3. Next-generation sequencing (NGS) technologies
Technology Limitations
WES Focuses on Efficiently Limited to The advent of NGS technologies has significantly improved
protein-coding identifies exons, may miss the speed, accuracy, and accessibility of genetic diagnoses.
regions disease-causing non-coding This technology allows for comprehensive analysis of the
mutations mutations ABCA12 gene and other relevant genomic regions, even
Genotype- Correlates Predicts disease Requires in neonates. Early detection of pathogenic mutations
10
phenotype mutations severity, guides comprehensive through NGS facilitates timely interventions and the
analysis with clinical treatments datasets
outcomes development of personalized treatment plans, improving
Functional Assesses impact Enhances May have limited patient outcomes. Moreover, the scalability of NGS enables
prediction of mutations on understanding accuracy for novel large-scale studies, contributing to a broader understanding
tools proteins of molecular mutations of HI and similar genetic disorders. 11
mechanisms
By integrating bioinformatics, WES, and NGS,
NGS Comprehensive Rapid, accurate, High cost, data researchers and clinicians are better equipped to tackle the
genomic and applicable interpretation
analysis to neonates complexity challenges of diagnosing and managing genetic diseases
Abbreviations: HI: Harlequin ichthyosis; NGS: Next-generation like HI. These tools not only enhance diagnostic accuracy
sequencing; WES: Whole-exome sequencing. but also pave the way for personalized medicine and
targeted therapies.
into the potential severity of the disease. For instance, 4. Current therapeutic approaches in HI
certain mutations in the ABCA12 gene are associated with
more severe clinical manifestations, enabling clinicians to The management of HI has evolved significantly over the
predict disease outcomes and tailor treatment strategies past few decades, largely due to advancements in neonatal
accordingly. Beyond variant calling, however, WES care and a deeper understanding of the disease’s genetic
4
12
pipelines must handle large-scale genomic datasets, basis. While there is no definitive cure for HI, several
requiring tools like GATK for variant filtering and treatment strategies have been developed to manage
ANNOVAR for annotation, ensuring robust data quality symptoms and improve the quality of life for affected
13
control. 8-10 individuals. In the following sections, we expand on the
primary therapeutic approaches and explore additional
3.2. Genotype-phenotype correlations and emerging strategies. These comparisons are summarized
functional predictions in Table 2.

One of the key strengths of bioinformatics lies in its 4.1. Neonatal care in HI
ability to establish genotype–phenotype correlations. By
analyzing genetic data, researchers can determine how Effective neonatal management is critical for HI survival.
specific mutations influence disease severity and clinical Immediate placement in humidified incubators (60 – 80%
9
presentation. In the case of HI, bioinformatics tools can humidity) reduces life-threatening fluid loss and electrolyte
3,12
predict the functional consequences of ABCA12 mutations, imbalances. Prophylactic antibiotics (e.g., ampicillin/
providing insights into how these alterations disrupt gentamicin) and ceramide-based emollients mitigate
lipid transport and epidermal differentiation. These tools infection risk and partial barrier restoration. 12-15 Nutritional
include PolyPhen-2 and SIFT, which typically analyze support via nasogastric tubes addresses hypermetabolic
missense variants and predict pathogenicity based on demands, while non-adhesive dressings minimize skin
evolutionary conservation and structural disruption. For trauma. 16-18 Despite improved survival (>50%), challenges
8,9
novel variants, AlphaFold-generated ABCA12 structures persist due to the lack of standardized protocols and long-
model atomic-level impacts, such as ATP-binding term sequelae. 12,18 Rapid WES in neonatal intensive care
domain destabilization, while MD simulations (molecular units may enable mutation-specific care, such as tailored
dynamics) assess lipid-binding affinity changes. In lipid formulations. 4,10
10
addition, tools such as KEGG and Reactome map
ABCA12 variants to disrupted lipid metabolism pathways, 4.2. Topical treatments
clarifying how mutations alter ceramide biosynthesis and Topical treatments remain the cornerstone therapies
epidermal barrier formation. These tools collectively for managing the characteristic skin abnormalities
6,9

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