We report a four-generation Pakistani kindred in which 11 members were affected with PPKS.
Based on previous reports of DSG1 mutations in PPKS, we performed direct DNA sequencing analysis.
Clinically, these patients presented with hyperkeratotic palms and with linear hyperkeratosis on the fingers. Additionally, focal hyperkeratosis was seen on the sole of the toes as well as the ball and heel of the foot. DNA sequencing analysis revealed a heterozygous G-to-T transversion in the 3′ splice acceptor site of intron 11 of the DSG1 gene designated 1688 −1 G > T. We predict that this mutation will lead to the skipping of exon 12 which is out of frame (134 nt), subsequent degradation of the mutant mRNA by non-sense mediated RNA decay, and haploinsufficiency for DSG1.
We report a novel splice site mutation in the DSG1 gene in PPKS, which further underscores the significance of the desmoglein gene family in diseases of epidermal integrity.