Novel mutation (Mangera-E288V) in alpha-1 antitrypsin deficiency

Giorgio Lorini; Stefania Ottaviani; Ilaria Giana; Giulia Accordino; Alice Maria Balderacchi; Angelo Guido Corsico; Ilaria Ferrarotti; Davide Piloni

doi:10.5826/mrm.2026.1053

Novel mutation (Mangera-E288V) in alpha-1 antitrypsin deficiency

Authors

Giorgio Lorini Unit of Respiratory Diseases, Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, Pavia, Italy,
Stefania Ottaviani Center for the Diagnosis of Inherited Alpha1-Antitrypsin Deficiency, Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo
Ilaria Giana Unit of Respiratory Diseases, Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, Pavia, Italy
Giulia Accordino Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy
Alice Maria Balderacchi Center for the Diagnosis of Inherited Alpha1-Antitrypsin Deficiency, Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo,
Angelo Guido Corsico Unit of Respiratory Diseases, Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, Pavia, Italy, Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy, Member of ERN-LUNG
Ilaria Ferrarotti Unit of Respiratory Diseases, Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, Pavia, Italy, 2 Center for the Diagnosis of Inherited Alpha1-Antitrypsin Deficiency, Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Member of ERN-LUNG
Davide Piloni Unit of Respiratory Diseases, Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, Pavia, Italy, Unit of Respiratory Diseases, Cardiothoracic and Vascular Department, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy

DOI: https://doi.org/10.5826/mrm.2026.1053

Keywords:

Alpha-1 antitrypsin deficiency, genotype, rare allele, clinical manifestations

Abstract

Background: Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. Several mutations have been described associated with the development of pulmonary and/or chronic liver diseases. We report a novel mutation M_angera, identified for the first time in an Italian patient originating from the city of Angera (Varese), Italy.
Case presentation: This case report describes a 64-year-old Italian male, a lifelong non-smoker, diagnosed with severe alpha-1 antitrypsin deficiency (AATD) as composed heterozygous with S allele and a novel mutation named M_angera. The patient presented with exertional dyspnea and had reduced serum AAT levels (0.54 g/L). Pulmonary function tests indicated mild airway obstruction with preserved diffusion capacity, and chest CT scans revealed early centrilobular emphysema and fibrotic changes. Genetic analysis was performed, finding a previously unreported mutation. Despite the severe AAT deficiency, the patient exhibited no significant clinical, radiological, or functional deterioration. Given the absence of disease progression, augmentation therapy was deferred in favor of ongoing annual monitoring.
Conclusions: This case report highlights the necessity of referring patients to specialized centers equipped with the expertise and tools required for precise diagnosis. Furthermore, the identification of the M_angera mutation expands the spectrum of known SERPINA1 variants associated with severe AATD, emphasizing the ongoing need for vigilance and thorough investigation in cases of suspected deficiency.

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