Multiplex epithelium dysfunction due to CLDN10 mutation: the HELIX syndrome

Area of Science:

• Genetics
• Molecular Biology
• Dermatology

Background:

• HELIX syndrome presents with hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia.
• The genetic underpinnings of HELIX syndrome remained largely unknown prior to this study.

Purpose of the Study:

• To identify the genetic cause of HELIX syndrome.
• To comprehensively characterize the clinical phenotype associated with HELIX syndrome.

Main Methods:

• Homozygosity mapping and whole-genome sequencing were employed in affected families.
• Gene sequencing, expression studies, functional assays, and histological analyses were performed.
• Protein bioinformatics was utilized to understand the impact of mutations.

Main Results:

• Biallelic missense mutations in CLDN10B were identified in six patients from two families.
• Mutations in CLDN10B, encoding Claudin-10b, led to impaired tight junction function.
• Patients exhibited hypohidrosis, renal NaCl loss, hypokalemia, hypolacrymia, ichthyosis, xerostomia, and enamel defects.

Conclusions:

• Mutations in CLDN10B are the genetic cause of HELIX syndrome.
• CLDN10B dysfunction disrupts tight junctions in multiple tissues, affecting renal ion transport and ectodermal gland function.
• The findings provide insights into epidermal integrity and gland homeostasis.