Identification of a novel alpha1-antitrypsin variant
Alpha-1-antitrypsin deficiency (A1ATD) is a genetic condition caused by SERPINA1 mutations, which results into decreased protease inhibitor activity in the serum and predisposes to emphysema and/or to liver disease due to accumulation of the abnormal protein in the hepatic cells. In most cases the c...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-01-01
|
| Series: | Respiratory Medicine Case Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221300711630123X |
| _version_ | 1819161762013904896 |
|---|---|
| author | Camille de Seynes C. Ged H. de Verneuil N. Chollet M. Balduyck C. Raherison |
| author_facet | Camille de Seynes C. Ged H. de Verneuil N. Chollet M. Balduyck C. Raherison |
| author_sort | Camille de Seynes |
| collection | DOAJ |
| description | Alpha-1-antitrypsin deficiency (A1ATD) is a genetic condition caused by SERPINA1 mutations, which results into decreased protease inhibitor activity in the serum and predisposes to emphysema and/or to liver disease due to accumulation of the abnormal protein in the hepatic cells. In most cases the clinical manifestations of A1ATD are associated with PIZZ (p.Glu366Lys; p.Glu366Lys (p.Glu342Lys; p.Glu342Lys)) or PISZ (p.Glu288Val; p.Glu366Lys (p.Glu264Val; p.Glu342Lys)) genotype, less frequently, deficient or null alleles may be present in compound heterozygous or homozygous A1AT deficient patients.
We report the identification of a novel alpha1-antitrypsin variant in a 64-year old woman presenting with dyspnea on exertion. Imaging revealed bilateral bronchiectasis associated with moderate panacinar emphysema. The pulmonary function tests (PFTs) were subnormal but hypoxemia was noticed and A1AT quantitative analysis revealed a severe deficiency. DNA sequencing showed compound heterozygosity for the PIZ variant and a novel missense variant p.Phe232Leu (p.Phe208Leu). No specific treatment was proposed since PFTs were within the normal range at this stage of the disease. Close follow-up of pulmonary and hepatic parameters was recommended. |
| first_indexed | 2024-12-22T17:17:29Z |
| format | Article |
| id | doaj.art-b22fcb9ac5ee4e038b7f9efc1486df5c |
| institution | Directory Open Access Journal |
| issn | 2213-0071 |
| language | English |
| last_indexed | 2024-12-22T17:17:29Z |
| publishDate | 2017-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Respiratory Medicine Case Reports |
| spelling | doaj.art-b22fcb9ac5ee4e038b7f9efc1486df5c2022-12-21T18:18:56ZengElsevierRespiratory Medicine Case Reports2213-00712017-01-0120C646710.1016/j.rmcr.2016.11.008Identification of a novel alpha1-antitrypsin variantCamille de Seynes0C. Ged1H. de Verneuil2N. Chollet3M. Balduyck4C. Raherison5Department of Respiratory Diseases, Bordeaux University, FranceDepartment of Biochemistry and Molecular Biology, Bordeaux University, FranceDepartment of Biochemistry and Molecular Biology, Bordeaux University, France130 rue de Pessac, 33000 Bordeaux, FranceDepartment of Biochemistry and Molecular Biology, Lille University, FranceDepartment of Respiratory Diseases, Bordeaux University, FranceAlpha-1-antitrypsin deficiency (A1ATD) is a genetic condition caused by SERPINA1 mutations, which results into decreased protease inhibitor activity in the serum and predisposes to emphysema and/or to liver disease due to accumulation of the abnormal protein in the hepatic cells. In most cases the clinical manifestations of A1ATD are associated with PIZZ (p.Glu366Lys; p.Glu366Lys (p.Glu342Lys; p.Glu342Lys)) or PISZ (p.Glu288Val; p.Glu366Lys (p.Glu264Val; p.Glu342Lys)) genotype, less frequently, deficient or null alleles may be present in compound heterozygous or homozygous A1AT deficient patients. We report the identification of a novel alpha1-antitrypsin variant in a 64-year old woman presenting with dyspnea on exertion. Imaging revealed bilateral bronchiectasis associated with moderate panacinar emphysema. The pulmonary function tests (PFTs) were subnormal but hypoxemia was noticed and A1AT quantitative analysis revealed a severe deficiency. DNA sequencing showed compound heterozygosity for the PIZ variant and a novel missense variant p.Phe232Leu (p.Phe208Leu). No specific treatment was proposed since PFTs were within the normal range at this stage of the disease. Close follow-up of pulmonary and hepatic parameters was recommended.http://www.sciencedirect.com/science/article/pii/S221300711630123X |
| spellingShingle | Camille de Seynes C. Ged H. de Verneuil N. Chollet M. Balduyck C. Raherison Identification of a novel alpha1-antitrypsin variant Respiratory Medicine Case Reports |
| title | Identification of a novel alpha1-antitrypsin variant |
| title_full | Identification of a novel alpha1-antitrypsin variant |
| title_fullStr | Identification of a novel alpha1-antitrypsin variant |
| title_full_unstemmed | Identification of a novel alpha1-antitrypsin variant |
| title_short | Identification of a novel alpha1-antitrypsin variant |
| title_sort | identification of a novel alpha1 antitrypsin variant |
| url | http://www.sciencedirect.com/science/article/pii/S221300711630123X |
| work_keys_str_mv | AT camilledeseynes identificationofanovelalpha1antitrypsinvariant AT cged identificationofanovelalpha1antitrypsinvariant AT hdeverneuil identificationofanovelalpha1antitrypsinvariant AT nchollet identificationofanovelalpha1antitrypsinvariant AT mbalduyck identificationofanovelalpha1antitrypsinvariant AT craherison identificationofanovelalpha1antitrypsinvariant |