Monday, March 18, 2024

Alpha 1-Antitrypsin Deficiency (SERPINA1) genotype, total blood

Description, Method, Result Format and Reference values Modification

Test code: 2825
Mnemónic code: GA1AT

Effective update from 18/03/2024




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Description:
Alpha 1-Antitrypsin Deficiency (SERPINA1) genotype, total blood


Method:
Amplification Refractory Mutation System (ARMS-PCR)


Result format:   R1   Result



Reference Values:
Technique: Qualitative detection of Pi*S, Pi*Z and Pi*M (without variants) alleles of the Alpha-1 A gene (AAT) in peripheral whole blood by PCR-ARMS.
     
NOTE:
The congenital deficiency of alpha-1 AT is the most common genetic cause of increased risk of developing lung and liver disease. Most individuals affected by this deficit are carriers of Pi*ZZ or Pi*SZ genotypes.
     
 
     




































        Version of Test: 16
     


Description:
ALPHA-1-ANTITRYPSIN (PI*S and Pi*Z GENOTYPE), DEFICIENCY· SERPINA1 · RT-PCR


Method:
Multiplex PCR/Real-Time PCR


Result format:   R1   Sample
                 R2   Result


References Values:
Interpretation
Alpha-1-antitrypsin deficiency (AAT) is autosomal recessive inherited and it is the most common genetic cause for increased risk of developing lung and liver diseases.
PI*M allele is associated with an AAT normal activity and PI*Z allele is the most common variant that causes AAT deficiency (homozygosity is associated to high risk of both emphysema and liver disease). 
PI*SZ genotype presents a mildly increased risk of lung disease (not liver) while PI*SS genotype it is not related to none of them. PI*MS and PI*MZ genotypes might also be associated with a very low-moderate decrease in AAT serum levels which may confere (in case of Pi*MZ) a slightly increased risk for emphysema and, eventually, liver disease. 
This report should be evaluated by a specialist in the context of all available clinical and family information in conjunction with other laboratory findings. Genetic counselling is recommended.

Test method
DNA extraction followed by real-time PCR amplification (CE-IVD commercial method) for detection of SERPINA1 gene regions including variants PI*S (rs17580 c.863A>T p.Glu288Val according to reference sequence NM_000295.4; Glu264Val or Pi*S Allele according to traditional nomenclature), PI*Z (rs28929474 c.1096G>A p.Glu366Lys according to reference sequence NM_000295.4; Glu342Lys or Pi*Z Allele according to traditional nomenclature) related to alpha-1-antitrypsin congenital deficiency.

Test limitations
Variants other than those studied are not analyzed.
Normal/polymorphic genomic variation in the patient may interfere with variant detection in the sample.

References
Stoller et al. (2006, updated 2023). Gene Reviews.
Fregonese et al. (2008). Orphanet J Rare Dis, 3(16).
Brode et al. (2012). CMAJ, 184(12).
Strnad et al. (2020). NEJM 382;15.






             Version of Test: 17
     


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