ClinVar

In a patient with localized EBS of the Weber-Cockayne type (EBS1C; 131800), Chen et al. (1995) found a 417G-A transition in the KRT14 gene, resulting in a met119-to-ile (M119I) substitution.

Hu et al. (1997) reported a large 6-generation French-Portuguese family (Ta) with localized EBS (EBS1C) due to a heterozygous M119I mutation. Blistering began around 1 year of age and was limited to the hands and feet. There was disease exacerbation in the summer, and the disorder tended to decrease with age.

See also M119T (148066.0009) and M119V (148066.0022) for other mutations affecting the same codon. Noting the distinct EBS phenotypes resulting from different substitutions at the M119 residue, Cummins et al. (2001) suggested that a more severe phenotype might result from greater perturbation of coiled-coil interactions by replacement of the hydrophobic methionine with hydrophilic threonine, whereas with conversion to isoleucine or valine, hydrophobicity is maintained.

Homozygosity for M119I

In the family with EBS1C reported by Hu et al. (1997), one family member, born of a consanguineous union, was homozygous for the mutation. This patient had a more severe phenotype, with earlier onset, more generalized blistering, and involvement of the oral, vaginal, and anal mucosa. Since age 14, blistering has been limited to the hands and feet. The distal skin was scarred, all 10 toenails were missing, and small areas of palmar hyperkeratosis were present. Hu et al. (1997) concluded that this mutation acts as a 'partial dominant' in that heterozygotes have milder localized disease and homozygotes have a more severe disease.