Abnormal cornified cell envelope formation in mutilating palmoplantar keratoderma unrelated to epidermal differentiation complex.
Mutilating palmoplantar keratoderma represents a heterogeneous group of disorders, unified by characteristic mutilation of the fingers or toes, associated with palmoplantar keratoderma. Although loricrin gene mutations were recently reported in Vohwinkel's syndrome and erythrokeratoderma, the genetic basis of mutilating palmoplantar keratoderma is largely unexplored. We studied a family of non-Vohwinkel's syndrome, nonerythrokeratoderma mutilating palmoplantar keratoderma. The proband and his sister were similarly affected. Recessive inheritance was expected from the consanguineous family history. The patients had hyperkeratosis restricted to the palms and the soles. No other body sites were affected. Digital constriction was seen on all the fingers and the mutilation was severe on the distal interphalangeal region of several fingers. Histopathologically, hyperkeratosis without parakeratosis was seen in the lesional skin. Ultrastructural, immunohistochemical, and immunoelectron microscopic analyses revealed malformed cornified cell envelopes, the abnormal intracytoplasmic loricrin retention, and reduced deposition of loricrin to cornified cell envelopes. Involucrin and small proline-rich proteins 1 and 2 were normally distributed. Sequencing of the entire exons and exon-intron borders of loricrin gene of the patients excluded a mutation in loricrin DNA sequence. Linkage analysis excluded the possibility of causative mutation in the epidermal differentiation complex region of 1q21, including loricrin, involucrin, small proline-rich proteins, filaggrin, and trichohyalin. These data confirm the presence of non-Vohwinkel's syndrome mutilating palmoplantar keratoderma phenotype with abnormal loricrin cross-linking at the final stage of cornified cell envelope formation, which is caused by mutations outside the epidermal differentiation complex region.
Akiyama
M
M
Division of Dermatology, Kitasato Institute Hospital, Tokyo, Japan.
Christiano
A M
AM
Yoneda
K
K
Shimizu
H
H
D000328:Adult; D002454:Cell Differentiation; D002878:Chromosomes, Human, Pair 1; D004817:Epidermis / Q000473:pathology*; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D008565:Membrane Proteins; C064554:loricrin