GJB6 missense variant in a Labrador Retriever with paw pad hyperkeratosis

Area of Science:

• Veterinary Dermatology
• Genetics
• Molecular Biology

Background:

• Palmoplantar keratoderma (PPK) in humans and paw pad hyperkeratosis in animals involve thickened skin on extremities.
• Over 60 genes are linked to PPK, often due to inherited mutations affecting skin development.
• Acquired causes include trauma, infections, cancer, and inflammatory conditions.

Purpose of the Study:

• To investigate the genetic cause of hyperkeratosis in a Labrador Retriever with affected paw pads.
• To identify the specific genetic variant responsible for the canine phenotype.
• To compare the canine condition with human genetic skin disorders for functional insights.

Main Methods:

• Histological examination of affected paw pad skin.
• Whole genome sequencing of the affected dog.
• Comparison of sequencing data against a large cohort of control dogs.

Main Results:

• Histology revealed significant orthokeratotic hyperkeratosis of the stratum corneum.
• Whole genome sequencing identified a private de novo heterozygous missense variant in the GJB6 gene.
• The GJB6 variant was absent in the dog's parents and control dogs.

Conclusions:

• The identified GJB6 missense variant is strongly implicated as the cause of paw pad hyperkeratosis in the investigated Labrador Retriever.
• The canine phenotype shares similarities with human Clouston syndrome, caused by GJB6 mutations.
• This study enhances understanding of GJB6 gene function and its role in skin development across species.