A novel missense mutation L468Q of keratin 6a in pachyonychia congenita type 1.

BACKGROUND

Pachyonychia congenita is an autosomal dominant disorder that usually develops in early infancy. The major features of the syndrome are hypertrophic nail dystrophy, palmoplantar keratoderma and oral leucokeratosis, accompanied by other ectodermal defects, according to subtype.

OBJECTIVE

To analyse the K6a gene mutation in a sporadic Chinese patient with pachyonychia congenita type 1 (PC-1) and to explore the relationship between the genotype and phenotype of PC-1.

METHODS

Genomic DNA was extracted from peripheral blood of the patient with PC-1 and 100 unrelated controls. The whole coding region of K6a gene was amplified using long-range polymerase chain reaction (PCR); nested PCR was then used to amplify the mutation 'hot-spot' of the K6a gene. The PCR products were directly sequenced to detect the mutation.

RESULTS

A novel missense mutation L468Q in the helix 2B domain of the K6a polypeptide was identified in the patient but not in the healthy individuals from the family and 100 unrelated control individuals.

CONCLUSIONS

We describe this mutation for the first time, and provide further evidence that the helix boundary motif sequences of K6a are a mutation 'hot-spot'.