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- Kremer, B, et al.
(author)
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A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats.
- 1994
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 330:20, s. 1401-6
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Journal article (peer-reviewed)abstract
- BACKGROUND: Huntington's disease is associated with an expanded sequence of CAG repeats in a gene on chromosome 4p16.3. However, neither the sensitivity of expanded CAG repeats in affected persons of different ethnic origins nor the specificity of such repeats for Huntington's disease as compared with other neuropsychiatric disorders has been determined.METHODS: We studied 1007 patients with diagnosed Huntington's disease from 565 families and 43 national and ethnic groups. In addition, the length of the CAG repeat was determined in 113 control subjects with a family history of Alzheimer's disease (44 patients), schizophrenia (39), major depression (16), senile chorea (5), benign hereditary chorea (5), neuroacanthocytosis (2), and dentatorubropallidoluysian atrophy (2). The number of CAG repeats was also assessed in 1595 control chromosomes, with the size of adjacent polymorphic CCG trinucleotide repeats taken into account.RESULTS: Of 1007 patients with signs and symptoms compatible with a diagnosis of Huntington's disease, 995 had an expanded CAG repeat that included from 36 to 121 repeats (median, 44) (sensitivity, 98.8 percent; 95 percent confidence interval, 97.7 to 99.4 percent). There were no significant differences among national and ethnic groups in the number of repeats. No CAG expansion was found in the 110 control subjects with other neuropsychiatric disorders (specificity, 100 percent; 95 percent confidence interval, 95.2 to 100 percent). In 1581 of the 1595 control chromosomes (99.1 percent), the number of CAG repeats ranged from 10 to 29 (median, 18). In 12 control chromosomes (0.75 percent), intermediate-sized CAG sequences with 30 to 35 repeats were found, and 2 normal chromosomes unexpectedly had expanded CAG sequences, of 39 and 37 repeats.CONCLUSIONS: CAG trinucleotide expansion is the molecular basis of Huntington's disease worldwide and is a highly sensitive and specific marker for inheritance of the disease mutation.
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| 2. |
- Lindqvist, Ulla, et al.
(author)
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Seven different assays of hyaluronan compared for clinical utility
- 1992
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In: Clinical Chemistry. - 0009-9147 .- 1530-8561. ; 38:1, s. 127-132
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Journal article (peer-reviewed)abstract
- To compare six assays of hyaluronan (hyaluronic acid; HYA) in serum, developed in different laboratories, we analyzed 10 samples from each of three groups: healthy persons, patients with primary biliary cirrhosis, and patients with rheumatoid arthritis. All the assays are based on the use of affinity proteins specific for HYA, prepared from cartilage or brain tissue, and are analogous to RIA or enzyme immunoassay techniques. The assay results were of the same magnitude. Although statistical analysis indicated that the methods in some cases deviated significantly from one another, this variation was less than the physiological variation in the healthy population. Therefore, the results of clinical investigations in which the various methods have been used are comparable. The analyses have high specificity and sensitivity for primary biliary cirrhosis but are somewhat less suitable for detecting rheumatoid arthritis. A seventh laboratory, which obtained antibodies to HYA, used these in an RIA to analyze a separate series of serum specimens. Results were in agreement with those obtained by one of the other assays.
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