Are X-linked cutis laxa and Menkes disease allelic?

It has been proposed that X-linked cutis laxa is a primary defect of copper transport and may in fact be allelic to Menkes syndrome. Several lines of evidence support this hypothesis. Serum ceruloplasmin and copper concentrations are decreased, and copper concentrations are elevated in cultured skin fibroblasts of patients and heterozygotes. These biochemical findings are strikingly similar to those of another disorder of copper metabolism--Menkes disease. The secondary reduction of lysyl oxidase in Menkes disease is comparable to the seen in X-linked cutis laxa. It is now possible to dissect the relationship between these two disorders. This gene encodes a 1,500 amino acid protein with features of a P-type copper-transporting ATPase. The cDNA detects an 8.5 kilobase transcript which is absent, markedly reduced, or altered in size in cell lines from many Menkes patients. Using our cDNA probe, designated Mc1, we asked whether expression of this gene was abnormal in cells from two patients with X-linked cutis laxa. The data suggest a role for the Mc1 gene product in X-linked cutis laxa, but do not explain the divergent phenotypes of this disorder and Menkes disease. Further studies should reveal the relationship between these two disorders.