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Contains fulltext : 81709.pdf (Publisher’s version ) (Closed access) The X-linked dominant trait focal dermal hypoplasia (FDH, Goltz syndrome) is a developmental defect with focal distribution of affected tissues due to a block of Wnt signal transmission from cells carrying a detrimental PORCN mutation on an active X-chromosome. Molecular characterization of 24 unrelated patients from different ethnic backgrounds revealed 23 different mutations of the PORCN gene in Xp11.23. Three were microdeletions eliminating PORCN and encompassing neighboring genes such as EBP, the gene associated with Conradi-Hunermann-Happle syndrome (CDPX2). 12/24 patients carried nonsense mutations resulting in loss of function. In one case a canonical splice acceptor site was mutated, and 8 missense mutations exchanged highly conserved amino acids. FDH patients overcome the consequences of potentially lethal X-chromosomal mutations by extreme skewing of X-chromosome inactivation in females, enabling transmission of the trait in families, or by postzygotic mosaicism both in male and female individuals. Molecular characterization of the PORCN mutations in cases diagnosed as Goltz syndrome is particularly relevant for genetic counseling of patients and their families since no functional diagnostic test is available and carriers of the mutation might otherwise be overlooked due to considerable phenotypic variability associated with the mosaic status.

In polyacrylamide gel gradient electrophoresis, serum and blister fluid of patients with bullous pemphigoid showed a nearly identical protein distribution pattern except for one more concentrated fraction in the blister fluid. This fraction could be isolated by several gel chromatographic steps and then be characterized as a protein with a molecular weight of 240,000 (BFP 240,000) consisting of several subunits. Two of these subunits could be identified as C3 fragments and two other ones as basement membrane zone antigens (BMZ-Ag) by means of a modified Laurell technique. The molecular weight of the BFP 240,000 may be small enough to allow it to penetrate through the vessel wall into the blood circulation where, with the BMZ-antibodies (BMZ-Ag-BMZ-Ab-complexes can be formed. The occurrence of such immune complexes in the serum has been shown in a previous paper.

SUMMARY The activities of five lysosomal hydrolases were determined fluorometrically in the serum of patients with systemic sclerosis (PSS), systemic lupus erythematosus (SLE), dermatomyositis (DM), rheumatoid arthritis (RA), or Raynaud's disease (RD). In PSS the β-galactosidase activity was significantly increased compared with controls and the other connective tissue diseases. The β-N-acetyl-glucosaminidase was significantly increased in PSS, SLE and DM. In PSS both enzymes were more active in the early stage of the disease than later. These changes of enzyme pattern seem to be a relatively reliable marker for the differential diagnosis of PSS compared to other connective tissue diseases, especially for RD, in which the β-galactosidase activity was significantly decreased. Further work is required to determine whether these polysaccharide-degrading acid hydrolases play a role in the pathogenesis of PSS.

SUMMARY No tree anti-basement membrane antibodies were found in the sera of four patients with bullous pemphigoid, and no free anti-DNA antibodies in the sera of two patients with systemic lupus erythematosus. The sera were treated with 3 mol/l urea and by gel chromatography to separate these antibodies from any circulating complexes, and antibodies to basement membrane were detected by immunofluorescence and to DNA by the Farr technique. The appropriate antibodies were found in all the sera, indicating that failure to detect antibodies by routine procedures may be due to binding of the antibodies to soluble antigens, forming complexes in the sera.