Search results for " congenital disorders of glycosylation"
showing 2 items of 2 documents
Are the new genetic tools for diagnosis of Wilson disease helpful in clinical practice?
2020
Summary The diagnosis of Wilson disease is not always easy. For many patients, a combination of tests reflecting disturbed copper metabolism may be needed. Testing for ATP7B variants has become part of the routine diagnostic approach. The methods of genetic testing include analysis of the 21 coding exons and intronic flanking sequences, in which exons with recurrent variants would be prioritised depending on the mutation frequency in the local population. If sequencing the entire ATP7B gene cannot identify 2 variants and the suspicion for Wilson disease is high, after reviewing the clinical data, WES (whole-exome sequencing) or WGS (whole-genome sequencing) could be applied. A workflow base…
Heterodimerization of Two Pathological Mutants Enhances the Activity of Human Phosphomannomutase2
2015
The most frequent disorder of glycosylation is due to mutations in the gene encoding phosphomannomutase2 (PMM2-CDG). For this disease, which is autosomal and recessive, there is no cure at present. Most patients are composite heterozygous and carry one allele encoding an inactive mutant, R141H, and one encoding a hypomorphic mutant. Phosphomannomutase2 is a dimer. We reproduced composite heterozygosity in vitro by mixing R141H either with the wild type protein or the most common hypomorphic mutant F119L and compared the quaternary structure, the activity and the stability of the heterodimeric enzymes. We demonstrated that the activity of R141H/F119L heterodimers in vitro, which reproduces t…