A novel insertional mutation in loricrin in Vohwinkel's Keratoderma.
A mutation in the gene encoding loricrin has recently been reported in a subset of patients with Vohwinkel's Keratoderma manifesting an associated ichthyosiform dermatosis. We have studied a further kindred with this clinical phenotype. Microsatellite marker analysis was consistent with linkage to chromosome 1q21 and direct sequencing of loricrin identified a heterozygous mutation with an insertion of a T residue at codon 209. This mutation is predicted to produce a mutant protein with a frameshift of its terminal 107 amino acids and to be 22 amino acids longer than the wild-type protein due to a delayed termination codon. The only previously reported mutation is a G insertion producing a frameshift after codon 231. The novel mutation we report is likely to have a similar functional effect on cornified envelope formation, with disturbance of transglutaminase-mediated cross-linking of envelope components, and serves to confirm the predicted role of insertional mutations in Vohwinkel's Keratoderma associated with ichthyosis.
Armstrong
D K
DK
Division of Molecular Medicine, Queen's University Belfast, Northern Ireland, UK.
McKenna
K E
KE
Hughes
A E
AE
D000595:Amino Acid Sequence; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007057:Ichthyosis / Q000235:genetics*; D007645:Keratoderma, Palmoplantar / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010375:Pedigree; D010641:Phenotype
D008565:Membrane Proteins; C064554:loricrin