التفاصيل البيبلوغرافية
| العنوان: |
Improving the Laboratory Diagnosis of M-like Variants Related to Alpha1-Antitrypsin Deficiency |
| المؤلفون: |
Valentina Barzon, Stefania Ottaviani, Alice Maria Balderacchi, Alessandra Corino, Davide Piloni, Giulia Accordino, Manuela Coretti, Francesca Mariani, Angelo Guido Corsico, Ilaria Ferrarotti |
| المصدر: |
International Journal of Molecular Sciences; Volume 23; Issue 17; Pages: 9859 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2022 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
alpha1-antitrypsin, SERPINA1 gene, rare pathogenic variants, M wurzburg, M whitstable, laboratory diagnosis |
| جغرافية الموضوع: |
agris |
| الوصف: |
Alpha1-antitrypsin (AAT) is a serine protease inhibitor that is encoded by the highly polymorphic SERPINA1 gene. Mutations in this gene can lead to AAT deficiency (AATD), which is associated with an increased risk of lung and/or liver disease. On the basis of electrophoretic migration, AAT variants are named with capital letters; M (medium) signifies the normal protein. Among pathological variants, the M-like ones represent a heterogeneous group of rare allelic variants that exhibit the same electrophoretic pattern as the M wild-type protein, which makes them difficult to detect with routine methods. In order to avoid their misdiagnosis, the present study defines and validates effective methods for the detection of two pathogenic M-like variants, Mwurzburg and Mwhitstable. Comparison of protein phenotypes using isoelectric focusing of samples that presented the Mwurzburg variant, as revealed by exons 5 sequencing, identified a particular electrophoretic pattern amenable to the Mwurzburg protein. The specific phenotyping pattern was retrospectively validated, thus enabling the detection of 16 patients with Mwurzburg variant among the subjects already tested but not sequenced according to our diagnostic algorithm. The Mwhitstable allele was detected by intron 4 sequencing of SERPINA1 gene. Mwurzburg and Mwhitstable are often misdiagnosed and the introduction of diagnostic improvements can help the clinical management, especially in patients with established lung disease without any other reported risk factors. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Biochemistry; https://dx.doi.org/10.3390/ijms23179859 |
| DOI: |
10.3390/ijms23179859 |
| الاتاحة: |
https://doi.org/10.3390/ijms23179859 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.ECF049A1 |
| قاعدة البيانات: |
BASE |