Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fabry's disease is an X-linked inborn error of glycosphingolipid catabolism, resulting from a deficiency in alpha-galactosidase A (alpha-Gal A). A 56-year-old Japanese woman was at first suspected of having hypertrophic cardiomyopathy. The patient and her son had alpha-Gal A activity in leukocytes that was remarkably below the limit of controls. DNA analysis of the alpha-Gal A gene revealed a novel missense mutation at codon 19 in exon 1, resulting in leucine-to-proline substitution. As a result she was confirmed as a classic Fabry heterozygote. Recent advances in enzyme replacement therapy can reverse the storage of glycosphingolipids in Fabry's disease. Thus, in patients with cardiac hypertrophy, it is important to differentiate Fabry's disease from other causes of hypertrophy. Therefore, it is necessary to measure alpha-Gal A activity in all suspected cases and to analyze genetic abnormalities in heterozygotes.
 ...
PMID:Fabry disease female proband with clinical manifestations similar to hypertrophic cardiomyopathy. 1535 80

Functional requirements shaped proteins into globular structures. Under these structural constraints, which require both regular secondary structure and a hydrophobic core, protein aggregation is an unavoidable corollary to protein structure. However, as aggregation results in reduced fitness, natural selection will tend to eliminate strongly aggregating sequences. The analysis of distribution and variation of aggregation patterns in the human proteome using the TANGO algorithm confirms the findings of a previous study on several proteomes: the flanks of aggregation-prone regions are enriched with charged residues and proline, the so-called gatekeeper-residues. Moreover, in this study, we observed a widespread redundancy in gatekeeper usage. Interestingly, aggregating regions from key proteins such as p53 or huntingtin are among the most extensive "gatekept" sequences. As a consequence, mutations that remove gatekeepers could therefore result in a strong increase in disease-susceptibility. In a set of disease-associated mutations from the UniProt database, we find a strong enrichment of mutations that disrupt gatekeeper motifs. Closer inspection of a number of case studies indicates clearly that removing gatekeepers may play a determining role in widely varying disorders, such as van der Woude syndrome (VWS), X-linked Fabry disease (FD), and limb-girdle muscular dystrophy.
 ...
PMID:Protein sequences encode safeguards against aggregation. 1915 39