Characterization of three new SERPINA1 variants PiQ0Heidelberg II, PiQ0Heidelberg III and PiQ0Heidelberg IV in patients with severe alpha-1 antitrypsin deficiency
Background: The clinical and molecular characteristics of three patients with previously unreported SERPINA1 mutations associated with severe alpha-1 antitrypsin deficiency (AATD) are described. The pathophysiology of the chronic obstructive pulmonary disease (COPD) present in these patients was cha...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-01-01
|
| Series: | Respiratory Medicine Case Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213007123000333 |
| _version_ | 1827952988298149888 |
|---|---|
| author | Philipp Höger Martina Veith Timm Greulich Eldridge Limen Judith Brock Kai Schlamp Katharina Buschulte Maria A. Presotto Julia Carmen Schäfer Felix Herth Franziska C. Trudzinski |
| author_facet | Philipp Höger Martina Veith Timm Greulich Eldridge Limen Judith Brock Kai Schlamp Katharina Buschulte Maria A. Presotto Julia Carmen Schäfer Felix Herth Franziska C. Trudzinski |
| author_sort | Philipp Höger |
| collection | DOAJ |
| description | Background: The clinical and molecular characteristics of three patients with previously unreported SERPINA1 mutations associated with severe alpha-1 antitrypsin deficiency (AATD) are described. The pathophysiology of the chronic obstructive pulmonary disease (COPD) present in these patients was characterized through clinical, biochemical, and genetic examinations. Case presentations: Case 1: A 73-year-old male with bilateral centri-to panlobular emphysema and multiple increasing ventrobasal bullae and incomplete fissures, COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade III B), progressive dyspnea on exertion (DOE), AAT level of 0.1–0.2 g/L. Genetic testing revealed a unique SERPINA1 mutation: Pi*Z/c.1072C > T. This allele was designated PiQ0Heidelberg II. Case 2: A 47-year-old male with severely heterogenous centri-to panlobular emphysema concentrated in the lower lobes, COPD GOLD IV D with progressive DOE, AAT <0.1 g/L. He also had a unique Pi*Z/c.10del mutation in SERPINA1. This allele was named PiQ0Heidelberg III. Case 3: A 58-year-old female with basally accentuated panlobular emphysema, GOLD II B COPD, progressive DOE. AAT 0.1 g/L. Genetic analysis revealed Pi*Z/c.-5+1G > A and c.-472G > A mutations in SERPINA1. This variant allele was named PiQ0Heidelberg IV. Conclusions: Each of these patients had a unique and previously unreported SERPINA1 mutation. In two cases, AATD and a history of smoking led to severe lung disease. In the third case, timely diagnosis, and institution of AAT replacement stabilized lung function. Wider screening of COPD patients for AATD could lead to faster diagnosis and earlier treatment of AATD patients with AATD which could slow or prevent progression of their disease. |
| first_indexed | 2024-04-09T14:07:04Z |
| format | Article |
| id | doaj.art-e3b46e1afcc84b039db7ec835f51cb7f |
| institution | Directory Open Access Journal |
| issn | 2213-0071 |
| language | English |
| last_indexed | 2024-04-09T14:07:04Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Respiratory Medicine Case Reports |
| spelling | doaj.art-e3b46e1afcc84b039db7ec835f51cb7f2023-05-07T04:16:47ZengElsevierRespiratory Medicine Case Reports2213-00712023-01-0143101838Characterization of three new SERPINA1 variants PiQ0Heidelberg II, PiQ0Heidelberg III and PiQ0Heidelberg IV in patients with severe alpha-1 antitrypsin deficiencyPhilipp Höger0Martina Veith1Timm Greulich2Eldridge Limen3Judith Brock4Kai Schlamp5Katharina Buschulte6Maria A. Presotto7Julia Carmen Schäfer8Felix Herth9Franziska C. Trudzinski10Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), Heidelberg, GermanyUniversity Medical Center Giessen and Marburg, Philipps-University, Department of Medicine, Pulmonary and Critical Care Medicine, Member of the German Center for Lung Research (DZL), Marburg, GermanyUniversity Medical Center Giessen and Marburg, Philipps-University, Department of Medicine, Pulmonary and Critical Care Medicine, Member of the German Center for Lung Research (DZL), Marburg, GermanyDepartment of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), Heidelberg, GermanyDepartment of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), Heidelberg, GermanyDepartment of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at University Hospital Heidelberg, Heidelberg, GermanyDepartment of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), Heidelberg, GermanyDepartment of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), Heidelberg, GermanyDepartment of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), Heidelberg, GermanyDepartment of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), Heidelberg, GermanyDepartment of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), Heidelberg, Germany; Corresponding author.Department of Pneumology and Critical Care Medicine, Thoraxklinik, Translational Lung Research Center (TLRC-H), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.Background: The clinical and molecular characteristics of three patients with previously unreported SERPINA1 mutations associated with severe alpha-1 antitrypsin deficiency (AATD) are described. The pathophysiology of the chronic obstructive pulmonary disease (COPD) present in these patients was characterized through clinical, biochemical, and genetic examinations. Case presentations: Case 1: A 73-year-old male with bilateral centri-to panlobular emphysema and multiple increasing ventrobasal bullae and incomplete fissures, COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade III B), progressive dyspnea on exertion (DOE), AAT level of 0.1–0.2 g/L. Genetic testing revealed a unique SERPINA1 mutation: Pi*Z/c.1072C > T. This allele was designated PiQ0Heidelberg II. Case 2: A 47-year-old male with severely heterogenous centri-to panlobular emphysema concentrated in the lower lobes, COPD GOLD IV D with progressive DOE, AAT <0.1 g/L. He also had a unique Pi*Z/c.10del mutation in SERPINA1. This allele was named PiQ0Heidelberg III. Case 3: A 58-year-old female with basally accentuated panlobular emphysema, GOLD II B COPD, progressive DOE. AAT 0.1 g/L. Genetic analysis revealed Pi*Z/c.-5+1G > A and c.-472G > A mutations in SERPINA1. This variant allele was named PiQ0Heidelberg IV. Conclusions: Each of these patients had a unique and previously unreported SERPINA1 mutation. In two cases, AATD and a history of smoking led to severe lung disease. In the third case, timely diagnosis, and institution of AAT replacement stabilized lung function. Wider screening of COPD patients for AATD could lead to faster diagnosis and earlier treatment of AATD patients with AATD which could slow or prevent progression of their disease.http://www.sciencedirect.com/science/article/pii/S2213007123000333Chronic obstructive pulmonary diseaseEmphysemaSERPINA1Alpha-1 antitrypsin deficiency |
| spellingShingle | Philipp Höger Martina Veith Timm Greulich Eldridge Limen Judith Brock Kai Schlamp Katharina Buschulte Maria A. Presotto Julia Carmen Schäfer Felix Herth Franziska C. Trudzinski Characterization of three new SERPINA1 variants PiQ0Heidelberg II, PiQ0Heidelberg III and PiQ0Heidelberg IV in patients with severe alpha-1 antitrypsin deficiency Respiratory Medicine Case Reports Chronic obstructive pulmonary disease Emphysema SERPINA1 Alpha-1 antitrypsin deficiency |
| title | Characterization of three new SERPINA1 variants PiQ0Heidelberg II, PiQ0Heidelberg III and PiQ0Heidelberg IV in patients with severe alpha-1 antitrypsin deficiency |
| title_full | Characterization of three new SERPINA1 variants PiQ0Heidelberg II, PiQ0Heidelberg III and PiQ0Heidelberg IV in patients with severe alpha-1 antitrypsin deficiency |
| title_fullStr | Characterization of three new SERPINA1 variants PiQ0Heidelberg II, PiQ0Heidelberg III and PiQ0Heidelberg IV in patients with severe alpha-1 antitrypsin deficiency |
| title_full_unstemmed | Characterization of three new SERPINA1 variants PiQ0Heidelberg II, PiQ0Heidelberg III and PiQ0Heidelberg IV in patients with severe alpha-1 antitrypsin deficiency |
| title_short | Characterization of three new SERPINA1 variants PiQ0Heidelberg II, PiQ0Heidelberg III and PiQ0Heidelberg IV in patients with severe alpha-1 antitrypsin deficiency |
| title_sort | characterization of three new serpina1 variants piq0heidelberg ii piq0heidelberg iii and piq0heidelberg iv in patients with severe alpha 1 antitrypsin deficiency |
| topic | Chronic obstructive pulmonary disease Emphysema SERPINA1 Alpha-1 antitrypsin deficiency |
| url | http://www.sciencedirect.com/science/article/pii/S2213007123000333 |
| work_keys_str_mv | AT philipphoger characterizationofthreenewserpina1variantspiq0heidelbergiipiq0heidelbergiiiandpiq0heidelbergivinpatientswithseverealpha1antitrypsindeficiency AT martinaveith characterizationofthreenewserpina1variantspiq0heidelbergiipiq0heidelbergiiiandpiq0heidelbergivinpatientswithseverealpha1antitrypsindeficiency AT timmgreulich characterizationofthreenewserpina1variantspiq0heidelbergiipiq0heidelbergiiiandpiq0heidelbergivinpatientswithseverealpha1antitrypsindeficiency AT eldridgelimen characterizationofthreenewserpina1variantspiq0heidelbergiipiq0heidelbergiiiandpiq0heidelbergivinpatientswithseverealpha1antitrypsindeficiency AT judithbrock characterizationofthreenewserpina1variantspiq0heidelbergiipiq0heidelbergiiiandpiq0heidelbergivinpatientswithseverealpha1antitrypsindeficiency AT kaischlamp characterizationofthreenewserpina1variantspiq0heidelbergiipiq0heidelbergiiiandpiq0heidelbergivinpatientswithseverealpha1antitrypsindeficiency AT katharinabuschulte characterizationofthreenewserpina1variantspiq0heidelbergiipiq0heidelbergiiiandpiq0heidelbergivinpatientswithseverealpha1antitrypsindeficiency AT mariaapresotto characterizationofthreenewserpina1variantspiq0heidelbergiipiq0heidelbergiiiandpiq0heidelbergivinpatientswithseverealpha1antitrypsindeficiency AT juliacarmenschafer characterizationofthreenewserpina1variantspiq0heidelbergiipiq0heidelbergiiiandpiq0heidelbergivinpatientswithseverealpha1antitrypsindeficiency AT felixherth characterizationofthreenewserpina1variantspiq0heidelbergiipiq0heidelbergiiiandpiq0heidelbergivinpatientswithseverealpha1antitrypsindeficiency AT franziskactrudzinski characterizationofthreenewserpina1variantspiq0heidelbergiipiq0heidelbergiiiandpiq0heidelbergivinpatientswithseverealpha1antitrypsindeficiency |