Connecting with connexins

Area of Science:

• Genetics
• Dermatology
• Otolaryngology

Background:

• Congenital sensorineural deafness is a common genetic disorder.
• Palmoplantar keratoderma (PPK) is a group of skin disorders affecting the palms and soles.
• Connexin 26 (GJB2) gene mutations are a frequent cause of non-syndromic sensorineural deafness.

Observation:

• An 18-year-old woman with congenital sensorineural deafness presented with asymptomatic thickening of the skin on her hands and feet.
• Examination revealed palmoplantar keratoderma without pseudoainhum.
• Genetic analysis identified a paternally inherited p.Asp46Glu mutation and a maternally inherited M34T variant in the connexin 26 gene.

Findings:

• The patient carried a paternally inherited pathogenic mutation (p.Asp46Glu) and a maternally inherited M34T variant in the connexin 26 gene.
• The p.Asp46Glu mutation is associated with autosomal dominant non-syndromic deafness.
• The M34T variant, typically considered non-pathogenic or causing a mild phenotype, may contribute to the patient's mild cutaneous presentation when combined with p.Asp46Glu.

Implications:

• This case suggests that combined connexin 26 gene variants can lead to a milder, later-onset phenotype of palmoplantar keratoderma.
• Understanding these complex genetic interactions is crucial for accurate diagnosis and genetic counseling in syndromic deafness.
• Further research into connexin 26 variant combinations may reveal new insights into genotype-phenotype correlations.