The molecular pathology of progressive symmetric erythrokeratoderma: a frameshift mutation in the loricrin gene and perturbations in the cornified cell envelope.
The erythrokeratodermas (EKs) are a group of disorders characterized by erythematous plaques associated with variable features that include palmoplantar keratoderma. One type of EK is known as "progressive symmetric erythrokeratoderma" (PSEK). We studied members of a family of Japanese origin in which the index case with PSEK had had well-demarcated nonmigratory erythematous plaques on her extremities since birth. Sequence determination of the loricrin gene revealed an insertion of a C following nucleotide 709. The mutation results in a frameshift that changes the terminal 91 amino acids in the wild-type polypeptide into missense amino acids and adds 65 additional residues. This further implicates loricrin defects in the pathogenesis of disorders with palmoplantar keratoderma and pseudoainhum.
Ishida-Yamamoto
A
A
Department of Dermatology, Asahikawa Medical College, Japan.
McGrath
J A
JA
Lam
H
H
Iizuka
H
H
Friedman
R A
RA
Christiano
A M
AM
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D004252:DNA Mutational Analysis; D003873:Dermatitis, Exfoliative / Q000235:genetics* / Q000473:pathology; D004817:Epidermis / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D006801:Humans; D007564:Japan; D007642:Keratosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D012867:Skin / Q000737:chemistry / Q000473:pathology
D008565:Membrane Proteins; C064554:loricrin