A simple screening test for variant transthyretins associated with familial transthyretin amyloidosis using isoelectric focusing
| Autor: | J. Skare, Thomas Ericsson, Lawreen H. Connors, Lee Anna Jones, Martha Skinner, W. David Lewis |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Population Biology Gene mutation Liver transplantation Transthyretin Gastroenterology Amyloid disease Internal medicine medicine Humans Prealbumin Family education Molecular Biology education.field_of_study Isoelectric focusing Amyloidosis nutritional and metabolic diseases medicine.disease Blood proteins Molecular biology Genetic Techniques Mutation biology.protein Molecular Medicine Isoelectric Focusing |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1407:185-192 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/s0925-4439(98)00037-4 |
| Popis: | Variant forms of the plasma protein transthyretin (TTR) are associated with the most frequently occurring type of familial systemic amyloidosis. Organ system involvement in transthyretin type amyloidosis (ATTR) is often similar to that which occurs in light chain amyloid disease (AL). The proper diagnosis of ATTR is important since treatment (liver transplantation) differs from that in AL (chemotherapy). We present a two-step test to screen sera for variant TTRs using non-denaturing gel electrophoresis performed in 7.5% acrylamide (PAGE) followed by isoelectric focusing (IEF) between pH 4.0 and 7.0 in 2.5 M urea. Serum samples from 110 patients with amyloidosis and their relatives were tested using this IEF technique and compared to genetic mutation results. Sera from patients with ATTR who underwent liver transplantation were also examined prior to and following surgery. IEF analysis showed the presence of both wild-type and variant TTR in 74 of the 110 serum samples tested. Genomic DNA from peripheral blood was used to identify TTR gene mutations in 77 of the 110 patients. Fifteen variants including Val122Ile, preponderant in the African-American population, could be demonstrated by IEF. The sensitivity of IEF was 96% (74/77) and the specificity was 100% (33/33). The predictive values for a positive or negative result were 100% (74/74) and 92% (33/36), respectively. There were no false-positive results and 4% (3/77) false-negative results. In sera from patients with ATTR who underwent liver transplantation, variant TTR was detected by IEF before, but not after, surgery. A simple, accurate, sensitive method is presented as a useful screening test for variant transthyretins associated with ATTR. |
| Databáze: | OpenAIRE |
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