Clinical and genetic insights into ABCA12 variants in three Chinese families with ichthyosis: Genotype–phenotype correlation

Autosomal recessive congenital ichthyosis (ARCI) comprises a series of non-syndromic ichthyoses. Pathogenic variants in several genes associated with ARCI have so far been identified. Notably, the variants in ABCA12 play a pivotal role in the pathology of ARCI. In this study, we report three Chinese families with compound heterozygous variants in the ABCA12 gene, including two novel variants and four reported variants. Clinical and genetic analyses were conducted to explore the genotype–phenotype correlation among the patients. Immunohistochemistry and transcriptome sequencing were utilized to assess the impact of pathogenic ABCA12 variants on skin homeostasis, revealing decreased levels of ABCA12 and claudin-1, alongside increased levels of involucrin and S100A8. In conclusion, our findings contribute to updating the genotype–phenotypic correlation and provide additional evidence for the long-term use of retinoic acid drugs in patients with causative ABCA12 variants.