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Retinitis pigmentosa, cutis laxa and pseudoxanthoma elasticum-like skin manifestations associated with GGCX mutations
Journal Contribution - Journal Article
GGCX mutations have been reported in patients with a pseudoxanthoma elasticum (PXE)-like phenotype, loose redundant skin, with multiple Vitamin K-dependent coagulation factor deficiencies. We report on the clinical findings and molecular results in 13 affected members of two families who had a uniform phenotype consisting of (PXE)-like skin manifestations in neck and trunk, loose sagging skin of trunk and upper limbs, and retinitis pigmentosa (RP) confirmed by ElectroRetinoGraphies in 10 affected individuals. There were no coagulation abnormalities. Molecular investigations of the ATP-Binding Cassette subfamily C member 6 (ABCC6) did not yield causative mutations. All 13 affected family members were found to be homozygous for the splice-site mutation c.373+3 G>T in the Gamma-Glutamyl carboxylase (GGCX) gene. All tested parents were heterozygous for the mutation, and healthy siblings were either heterozygous or had the wild-type. We suggest that the present patients represent a hitherto unreported phenotype associated with GGCX mutations. Di-genic inheritance has been suggested to explain the variability in phenotype in GGCX mutation carriers. Consequently, the present phenotype may not be explained only by the GGCX mutations only but may be influenced by variants in other genes or epigenetic and environmental factors.
Journal: Journal of Investigative Dermatology
Pages: 2331 - 2338