학술논문
Description of 22 new alpha-1 antitrypsin genetic variants
Document Type
Report
Author
Source
Orphanet Journal of Rare Diseases. September 17, 2018, Vol. 13 Issue 1
Subject
Language
English
ISSN
1750-1172
Abstract
Author(s): Céline Renoux[sup.1,2] , Marie-Françoise Odou[sup.3,4] , Guillaume Tosato[sup.3] , Jordan Teoli[sup.1] , Norman Abbou[sup.1] , Christine Lombard[sup.5] , Farid Zerimech[sup.3,6] , Nicole Porchet[sup.3] , Colette Chapuis Cellier[sup.5] , Malika [...]
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 (M1.sub.Cremeaux) 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 S.sub.Donosti (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. Keywords: Alpha-1 antitrypsin deficiency, SERPINA1 genotyping, Null alleles
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 (M1.sub.Cremeaux) 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 S.sub.Donosti (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. Keywords: Alpha-1 antitrypsin deficiency, SERPINA1 genotyping, Null alleles