Alpha-1 Antitrypsin Deficiency in a Young Never Smoker With Novel Pi*Null Homozygous Mutation: a Case Report

Igor Z Barjaktarevic; Andrew W Hong; Alyssa Hoover; Stanley Nelson; Said Isse; Semi Yoon; Mark Brantley

doi:10.15326/jcopdf.2024.0518

Alpha-1 Antitrypsin Deficiency in a Young Never Smoker With Novel Pi*Null Homozygous Mutation: a Case Report

Chronic Obstr Pulm Dis. 2024 Nov 22;11(6):624-629. doi: 10.15326/jcopdf.2024.0518.

Authors

Igor Z Barjaktarevic¹, Andrew W Hong², Alyssa Hoover³, Stanley Nelson³, Said Isse⁴, Semi Yoon¹, Mark Brantley⁵

Affiliations

¹ Division of Pulmonary and Critical Care Medicine, University of California, Los Angeles, California, United States.
² Department of Medicine, University of California, Los Angeles, California, United States.
³ Human Genetics, University of California, Los Angeles, California, United States.
⁴ Cleveland Clinic Abu Dhabi, Abu Dhabi,United Arab Emirates.
⁵ Division of Pulmonary and Critical Care Medicine, University of Florida, Gainesville, Florida, United States.

PMID: 39357506
DOI: 10.15326/jcopdf.2024.0518

Abstract

Alpha-1 antitrypsin (AAT) deficiency is an autosomal codominant disorder caused by SERPINA1 gene mutations. PI*Z and PI*S mutations commonly underlie this deficiency, but rarer homozygous PI*Null (Q0) mutations may result in a complete loss of AAT. Such rare mutations lead to severe AAT deficiency and early onset of lung disease. We present a case of a 35-year-old female never-smoker born to consanguineous parents who developed severe panlobular emphysema and end-stage respiratory insufficiency requiring lung transplantation. Subsequent genetic testing identified her as homozygous for a novel c.82del mutation-here named Q0_Bani-Yas based on the region of the primary carrier's origin-which resulted in undetectable levels of the AAT protein.

Keywords: Pi*Null; SERPINA1; alpha-1 antitrypsin deficiency; mutation.