Abstract

Background: The identification of the molecular basis of disorders of keratinisation has significantly advanced our understanding of skin biology, revealing new information on key structures in the skin, such as the intermediate filaments, desmosomes, and gap junctions. Among these disorders, there is an extraordinarily heterogeneous group known as palmoplantar keratodermas (PPK), for which only a few molecular defects have been described. A particular form of PPK, known as punctate PPK, has been described in a few large autosomal dominant pedigrees, but its genetic basis has yet to be identified.

Aim: Identification of the gene for punctate PPK.

Methods: Clinical examination and linkage analysis in three families with punctate PPK.

Results: A genomewide scan was performed on an extended autosomal dominant pedigree, and linkage to chromosome 15q22–q24 was identified. With the addition of two new families with the same phenotype, we confirmed the mapping of the locus for punctate PPK to a 9.98 cM interval, flanked by markers D15S534 and D15S818 (maximum two point lod score of 4.93 at θ = 0 for marker D15S988).

Conclusions: We report the clinical and genetic findings in three pedigrees with the punctate form of PPK. We have mapped a genetic locus for this phenotype to chromosome 15q22–q24, which indicates the identification of a new gene involved in skin integrity.