Description of 22 new alpha-1 antitrypsin genetic variants

Céline Renoux†,
Marie-Françoise Odou†Email author View ORCID ID profile,
Guillaume Tosato,
Jordan Teoli,
Norman Abbou,
Christine Lombard,
Farid Zerimech,
Nicole Porchet,
Colette Chapuis Cellier†,
Malika Balduyck† and
Philippe Joly†

†Contributed equally

Orphanet Journal of Rare Diseases201813:161

https://doi.org/10.1186/s13023-018-0897-0

Received: 26 April 2018
Accepted: 23 August 2018
Published: 17 September 2018

Abstract

Alpha-1 antitrypsin deficiency is an autosomal co-dominant disorder caused by mutations of the highly polymorphic SERPINA1 gene. This genetic disorder still remains largely under-recognized and can be associated with lung and/or liver injury. The laboratory testing for this deficiency typically comprises serum alpha-1 antitrypsin quantification, phenotyping according to the isoelectric focusing pattern and genotyping if necessary. To date, more than 100 SERPINA1 variants have been described and new genetic variants are frequently discovered. Over the past 10 years, 22 new genetic variants of the SERPINA1 gene were identified in the daily practice of the University Medical laboratories of Lille and Lyon (France). Among these 22 variants, seven were Null alleles and one with a M1 migration pattern (M1Cremeaux) was considered as deficient according to the clinical and biological data and to the American College of Medical Genetics and Genomics (ACMG) criteria. Three other variants were classified as likely pathogenic, three as variants of uncertain significance while the remaining ones were assumed to be neutral. Moreover, we also identified in this study two recently described SERPINA1 deficient variants: Trento (p.Glu99Val) and SDonosti(p.Ser38Phe). The current data, together with a recent published meta-analysis, represent the most up-to-date list of SERPINA1 variants available so far.