A novel mutation within the 2B rod domain of keratin 9 in a Chinese pedigree with epidermolytic palmoplantar keratoderma combined with knuckle pads and camptodactyly

Knuckle pads and camptodactyly are overlapping symptoms associated with many genetic and environmental factors. To the best of our knowledge, all reported cases of epidermolytic palmoplantar keratoderma (EPPK) with knuckle pads have been without accompanying camptodactyly. We here report a novel KRT9 mutation-EPPK family with combined knuckle pads and camptodactyly. All the EPPK-affected individuals in this southern Chinese pedigree suffered severe diffuse palmar and plantar hyperkeratosis including hyperhidrosis and cuticle splitting: 3 females presented EPPK only, 8 adult males had notably severe knuckle pads and camptodactyly as well as EPPK, and one 6-year-old boy manifested EPPK with knuckle pads. Haplotype analysis excluded the known candidate loci for camptodactyly and/or knuckle pad-like phenotypes on chromosomes 13q12, 3q11.2-q13.12, 1q24-q25, 4p16.3 and 16q11.1-q22, while only the markers D17S1787 and D17S579 flanking KRT9 showed co-segregation with EPPK. Then a novel c. T1373C (p.L458P) mutation within the sixth exon of KRT9 was validated, and this mutation presented a more severe pathogenicity than the previously reported p.L458F. We speculated that KRT9 plays a complicated role in the genesis of EPPK with knuckle pads and camptodactyly, which needs to be further investigated.