Phenotype-genotype correlation in a cohort of 15 patients with hereditary ichthyosis

Hereditary ichthyosis is a heterogeneous group of skin disorders classified within the Mendelian disorders of cornification (MEDOC). Its primary clinical manifestations include hyperkeratosis, dryness, and scaling as a result of desquamation. Due to symptomatic overlap with other keratinization disorders, accurate differential diagnosis is essential. Furthermore, genetic diagnosis of hereditary ichthyosis provides critical information for genetic counseling and informed reproductive decision-making for affected families.

In this study, we performed a comprehensive genetic analysis on 15 probands with clinically confirmed or suspected ichthyosis. Using whole-exome sequencing (WES) and chromosomal microarray analysis (CMA), we identified potential pathogenic variants, which were subsequently verified in family members using Sanger sequencing or Quantitative fluorescent PCR (QF-PCR). The functional impact of detected missense variants was assessed by analyzing the conservation of the affected amino acid residues using the MEGA7 software.

Our analysis revealed disease-associated variants in several genes, including FLG, STS, TGM1, and ABCA12. Notably, we identified four previously unreported variants: c.82 T > A (p.L28M) and c.9774C > A (p.H3258Q) in the FLG gene, and c.974C > T (p.S325F) and c.614 A > C (p.N205T) in the ABCA12 gene.

This study establishes a clear molecular diagnosis for the enrolled ichthyosis patients. The findings expand the known variant spectrum of hereditary ichthyosis, providing a solid basis for genetic counseling and valuable insights for future reproductive planning in these families.