Varied modes of onset make the early diagnosis of Wilson's disease difficult. A deficiency of serum ceruloplasmin, usually characteristic of the disease, was used as the basis for a screening test. Simple test materials and provision for handling about 50 plasma samples simultaneously made this test feasible for large-scale screening.The screening test was applied to 336 persons hospitalized for psychiatric disorders, to detect patients with Wilson's disease before the classical symptoms appeared. Two patients with ceruloplasmin levels below the normal limits were detected but did not have Wilson's disease. Further application of the screening test to relatives of patients known to have Wilson's disease and to individuals with any symptoms of the disease (hepatic disease, extrapyramidal dysfunction, psychiatric disorders, behaviour problems in children) would aid in early diagnosis and more effective treatment.

Adolescent↗

PubMed1966

Factors influencing serum ceruloplasmin levels in normal individuals.

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Adolescent↗

PubMedDate not supplied

DNA restriction fragments associated with alpha 1-antitrypsin indicate a single origin for deficiency allele PI Z.

The alpha 1-protease inhibitor, or alpha-antitrypsin (AAT), a major plasma inhibitor of leukocyte elastase and bacterial proteases, is encoded at the PI locus on chromosome 14 (14q24.3-q32.1). A deficiency of AAT in individuals homozygous for the PI Z allele occurs in about 1 in 2,000-8,000 caucasians and is associated with an increased risk of early adult onset emphysema and liver disease in childhood. We have now used DNA polymorphisms associated with the AAT gene to investigate the origin of the PI Z allele. Using two genomic probes extending into the 5' and 3' flanking regions, respectively, we have identified eight polymorphic restriction sites. Extensive linkage disequilibrium occurs throughout the probed region with the PI Z allele, but not with normal PI M alleles. The Z allele occurs mainly with one haplotype, indicating a single, relatively recent, origin in caucasians.

Alleles↗

PubMedDate not supplied

His1069Gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype.

In the present study we examined 33 German and 10 Cuban unrelated Wilson disease (WND) index patients and their relatives. The common His1069Gln mutation accounted for 42% of all WND chromosomes in the German series and the haplotype C was found to be highly predictive for this mutation. Six WND gene mutations have not been described previously and involved a splice site at intron 18 (3903 + del1G), a termination codon in the copper-binding region of exon 2 (Cys271X), and missense mutations in transmembrane region 2 (Gly710Ala), in transmembrane region 3 (Tyr741Cys), in the DKTGT motif (Thr1031Ile) and in the ATP loop region (Gly1176Arg). In 15 German WND index patients and three sibs both WND mutations could be determined and a genotype-phenotype correlation was attempted. Patients homozygous for the His1069Gln mutation showed almost the complete range of clinical presentations, and thus in our study this mutation is not associated with a late, neurological presentation.

Base Sequence↗

PubMedDate not supplied

A preliminary evaluation of the Gonozyme test.

Gonozyme is a solid-phase enzyme immunoassay that detects antigens of Neisseria gonorrhoeae in clinical specimens. The test was 100% sensitive and 96.8% specific when applied to 71 urethral specimens from men with symptomatic urethritis, and 89.5% specific for 19 urethral specimens from men examined after eradication of gonorrhea by antibiotics. For cervical specimens obtained before therapy from 368 women with gonorrhea, the Gonozyme test had a sensitivity of 88.5% and a specificity of 94.3%. The test was 100% specific when used for testing of 37 cervical specimens obtained after therapy of gonorrhea. The predictive values of a positive Gonozyme test were 90.5% for cervical specimens from women attending a sexually transmitted disease clinic and 97% for urethral specimens from men with urethritis. The predictive values of negative Gonozyme tests in these same circumstances were 100% for urethral specimens and 93.6% for cervical specimens.

Antigens, Bacterial↗

PubMedDate not supplied

Interaction between variant apolipoproteins C-II and E that affects plasma lipoprotein concentrations.

The genes for apolipoprotein (apo) C-II, a cofactor for activation of lipoprotein lipase, and apo E, a ligand for receptor-mediated uptake of triglyceride-rich lipoproteins, are physically linked on chromosome 19q13.1. In a large Caribbean Caucasian family, several individuals had clinical features of the complete absence of lipoprotein lipase activity and were homozygous for a DNA frameshift mutation of apo C-II, imparting functional inactivity to the mutant protein. Plasma from heterozygous carriers of this mutation, when compared with plasma from relatives who were noncarriers, had significantly diminished capacity to activate lipoprotein lipase in vitro. We also observed in heterozygotes for this mutation a wide range of serum lipid and lipoprotein levels. When age and sex were taken into account, the presence of a single apo E allele encoding the E4 isoform occurring in individuals with a single mutant apo C-II allele was strongly associated with higher levels of cholesterol, triglycerides, very low density lipoprotein cholesterol, and non-high density lipoprotein cholesterol when compared with those of relatives who carried neither or only one variant allele. This suggests that a single genetic mutation that usually has a recessive effect on lipoprotein metabolism can have an interactive effect on lipid phenotype when it is coinherited with a single mutation at another gene whose product affects the same metabolic pathway.

Adult↗