Mutations in the SLURP-1 gene underlie Mal de Meleda in three Pakistani families

Abstract

Mal de Meleda (MDM) (MIM #248300) is an autosomal recessive palmoplantar keratoderma (PPK). It is characterized clinically by erythematous hyperkeratotic plaques over palms and soles that start early in life and progress later in life in a transgradiens form associated with pain, macerations, foul odor, pseudoainhum, brachydactyly, onychodystrophy and perioral erythema. To look for SLURP-1 gene mutations in patients with MDM. We collected peripheral blood samples from Pakistani family members affected with MDM and 100 population-matched unrelated healthy control individuals in EDTA-containing tubes. All exons of the SLURP-1 gene with adjacent sequences at exon-intron borders were amplified. The amplified PCR products were directly sequenced in an ABI Prism 310 Automated Sequencer. Screening assay, using the restriction enzyme HphI was performed. We determined three mutations in the SLURP-1 gene: one novel mutation, c.Ivs1+1G>A, and two recurrent mutations, p.R96X and p.G86R. Screening assays for the novel mutation excluded the possibility of polymorphism. In vivo transcription assays showed that the mutation c.Ivs1+1G>A leads to aberrant splicing events. Our results expand the spectrum of mutations in SLURP-1 gene.