Title :

Alpha1-antitrypsin deficiency in Greece: Focus on rare variants.

Author(s) :

Papiris, S. A. [Auteur]
Université d'Athènes [UOA]
Veith, M. [Auteur]
Papaioannou, A. I. [Auteur]
Université d'Athènes [UOA]
Apollonatou, V. [Auteur]
Ferrarotti, I. [Auteur]
Ottaviani, S. [Auteur]
Tzouvelekis, A. [Auteur]
Tzilas, V. [Auteur]
Rovina, N. [Auteur]
Stratakos, G. [Auteur]
Gerogianni, I. [Auteur]
Daniil, Z. [Auteur]
Kolilekas, L. [Auteur]
Dimakou, K. [Auteur]
Pitsidianakis, G. [Auteur]
Tzanakis, N. [Auteur]
Tryfon, S. [Auteur]
Fragopoulos, F. [Auteur]
Antonogiannaki, E. M. [Auteur]
Lazaratou, A. [Auteur]
Fouka, E. [Auteur]
Papakosta, D. [Auteur]
Emmanouil, P. [Auteur]
Anagnostopoulos, N. [Auteur]
Karampitsakos, T. [Auteur]
Vlami, K. [Auteur]
Kallieri, M. [Auteur]
Lyberopoulos, P. [Auteur]
Loukides, S. [Auteur]
Bouros, D. [Auteur]
Bush, A. [Auteur]
Balduyck, Malika [Auteur]
Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
Lombard, C. [Auteur]
Université Claude Bernard Lyon 1 [UCBL]
Cottin, V. [Auteur]
Université Claude Bernard Lyon 1 [UCBL]
Mornex, J. F. [Auteur]
UMR INRA / ENV Lyon / Univ. Lyon 1 : Lentivirus des petits ruminants
Vogelmeier, C. F. [Auteur]
Greulich, T. [Auteur]
Manali, E. D. [Auteur]

Journal title :

Pulmonology

Publisher :

Elsevier

Publication date :

2023-02-14

ISSN :

2531-0437

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Purpose A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. Aim to investigate genotype and clinical profile of Greeks with AATD. Methods ...
Show more >Purpose A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. Aim to investigate genotype and clinical profile of Greeks with AATD. Methods Symptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. Results Included are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5–58.5) years, AAT-levels 0.20(0.08–0.26) g/L, FEV1(%predicted) 41.5(28.8–64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with MHeerlen (M1Ala/M1Val); p.(Leu65Pro) with MProcida; p.(Lys241Ter) with Q0Bellingham; p.(Leu377Phefs*24) with Q0Mattawa (M1Val) and Q0Ourem (M3); p.(Phe76del) with MMalton (M2), MPalermo (M1Val), MNichinan (V) and Q0LaPalma (S); p.(Asp280Val) with PLowell (M1Val); PDuarte (M4), YBarcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0GraniteFalls, Q0Saint-Etienne, Q0Amersfoort(M1Ala), MWürzburg, NHartfordcity and one novel-variant (c.1A>G) named Q0Attikon.Heterozygous included PI*MQ0Amersfoort(M1Ala), PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). Conclusion Genotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis. In the future the detection of rare genotypes may add to personalize preventive and therapeutic measures.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364

Submission date :

2023-06-05T06:49:10Z
2023-09-27T08:33:31Z