# Identification of Novel Mutation in the ABCA12 Gene Causing Harlequin Ichthyosis

## TL;DR

A new mutation in the ABCA12 gene was found in an Iranian infant with Harlequin ichthyosis, a severe skin condition, offering insights for genetic counseling and prenatal screening.

## Contribution

The study reports a novel homozygous mutation in the ABCA12 gene not previously associated with Harlequin ichthyosis.

## Key findings

- A novel homozygous mutation [c.4702_4706del] in the ABCA12 gene was identified in an Iranian infant with Harlequin ichthyosis.
- The mutation was found in a heterozygous state in asymptomatic parents, confirming autosomal recessive inheritance.
- The findings support the importance of genetic counseling and prenatal screening for families with a history of the disease.

## Abstract

Harlequin ichthyosis (HI) is an uncommon and extremely severe hereditary condition that primarily affects the skin. Infants born with this disorder display dense skin and prominent diamond‐shaped plates that cover a significant portion of their bodies. Infants with this disease have difficulty regulating body temperature and maintaining hydration, leading to respiratory failure and feeding problems, making them more vulnerable to infections. Most patients die shortly after birth because of these clinical symptoms. Scientific evidence has shown that a mutation in the ABCA12 gene is the principal underlying cause of HI. Using whole‐exome sequencing, we identified a novel mutation in an Iranian infant with HI. This case presented with characteristic cutaneous manifestations, leading to the discovery of a novel homozygous mutation in the ABCA12 gene. This specific mutation [c.4702_4706del, p.(Leu1568IlefsTer5)] has not been reported in any other cases of harlequin ichthyosis and was detected in a heterozygous state in asymptomatic parents. The insights gained from analyzing this family enhance our understanding of the disease's molecular origin, aid in carrier identification, support genetic counseling, and emphasize the importance of prenatal genetic screening for families with a history of HI.

Harlequin ichthyosis is a severe genetic skin disease caused by mutations in the ABCA12 gene. This study identifies a novel homozygous mutation in an Iranian infant. The asymptomatic parents were heterozygous carriers. The findings enhance disease understanding, facilitate carrier detection, and highlight the need for genetic counseling and prenatal screening.