Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations leading to hemophilia A by substitution of amino acids in coagulation factor VIII may provide important clues to the structure and function of this large and enigmatic protein. To efficiently find missense mutations, hemophiliacs with mild and moderately severe forms of the disease were surveyed. DNA samples from affected individuals were assayed for mutations by denaturing gradient gel electrophoresis following DNA amplification of target regions, which included all coding regions except for that of the dispensable B domain. Missense mutations were observed in 20 of the 34 patients examined, with identical mutations found in five pairs of patients. All mutations were found in the repetitive A and C domains. By aligning these domains in factor VIII with homologous domains in factor V, ceruloplasmin, and the mouse milk fat globule membrane protein, it was determined that most mutations change amino acids in areas of strong sequence conservation. Three additional mutations were detected, including a point mutation in an intron, a stop codon mutation, and a silent base change. Ten of the 18 different mutations discovered in this patient population are reported here for the first time.
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PMID:Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A. 130 32

In research on congenital metabolic disorders, a biochemist can choose between the theoretical and the practical approach. The diagnosis of metabolic diseases relies on 1) the determination of the presence of metabolites under normal conditions that are direct substrates of the defective enzyme (e.g., the Gm2 ganglioside in the brain tissue of a patient with Tay-Sachs disease); 2) the determination of the lack or insufficiency of the direct product of the defective enzyme (e.g., aryl sulfatase A in the cells of patients with metachromatic leukodystrophy), hormone (hypothyroidism), or receptor (congenital hypercholesterolemia); 3) determination of substance whose reduction was established by experimentation, but the cause of the decrease is not known (ceruloplasmin in Wilson's disease); and 4) DNA analysis. Metabolic impairment of genetic origin is not treatable. The disease can be prevented by 1) removing the inappropriate metabolite (e.g., copper accumulation can be avoided by giving penicillamine or zinc salts); 2) limiting those substances in the critical phase of childhood that are components of the defective enzyme (e.g. gluten reduction in colic and protein in phenylketonuria); 3) supplementing the insufficient metabolite (e.g., phosphate in hypophosphatemia by sound for 12 hours a day); 4) protecting the patients (e.g. from light in porphyria); and 5) treatment by substances (giving coagulation factor VIII in hemophilia and thyroid hormones in hypothyroidism). There is a dilemma in subjecting patients to a diagnosis of progression to Huntington's chorea 20 years in advance or informing them about the high risk of hereditary disease for the next child (25% for the recessive and 50% for the dominant mode). Ethical committees have usually opted for a recommendation of selective abortion in clear-cut cases. Increasingly refined diagnostic methods have magnified the responsibility of the biochemist.
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PMID:[Prenatal diagnosis: a chance? risk? dilemma?]. 209 55

A complete copy of the mRNA sequences encoding human coagulation factor VIII:C has been cloned and expressed. The DNA sequence predicts a single chain precursor of 2,351 amino acids with a relative molecular mass (Mr) 267,039. The protein has an obvious domain structure, contains sequence repeats and is structurally related to factor V and ceruloplasmin.
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PMID:Molecular cloning of a cDNA encoding human antihaemophilic factor. 643 28