Delayed-Onset Pachyonychia Congenita Caused by a Novel Mutation in the V2 Domain of Keratin 6B

In 2013, a study reported a Chinese female patient with delayed-onset Pachyonychia Congenita type 2 (PC-2), a rare autosomal-dominant ectodermal disorder characterized by nail dystrophy and other skin abnormalities. The patient, who was 9 years old, developed thickened fingernails and toenails at the age of 6, but did not exhibit other common symptoms of PC-2 such as steatocystoma multiplex, palmoplantar keratoderma, or natal teeth. Genetic testing revealed a novel heterozygous mutation (1495G-A) in exon 9 of the keratin 6b (K6b) gene, resulting in a glycine to serine substitution at codon 499 (G499S). This mutation was not found in her parents or in 100 unrelated control subjects. The study concluded that the patient's delayed-onset PC-2 was caused by this novel mutation in the V2 domain of K6b, and the findings contribute to the understanding of the relationship between genotype and phenotype in PC, potentially offering insights into the cause of phenotypic variability in the disorder.