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α-1 Antitrypsin Genotype-Phenotype Discrepancy in a 42-Year-Old Man Who Carries the Null-Allele (CROSBI ID 269601)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Pavičić, Tomislav ; Ćelap, Ivana ; Njegovan, Milena ; Tešija Kuna, Andrea ; Štefanović, Mario α-1 Antitrypsin Genotype-Phenotype Discrepancy in a 42-Year-Old Man Who Carries the Null-Allele // Laboratory medicine, 50 (2019), 3; 31583408, 7. doi: 10.1093/labmed/lmz059

Podaci o odgovornosti

Pavičić, Tomislav ; Ćelap, Ivana ; Njegovan, Milena ; Tešija Kuna, Andrea ; Štefanović, Mario

engleski

α-1 Antitrypsin Genotype-Phenotype Discrepancy in a 42-Year-Old Man Who Carries the Null-Allele

Background Alpha-1-antitrypsin (A1AT) deficiency is a hereditary condition caused by mutations in the SERPINA1 gene and associated with lung emphysema and liver disease. Laboratory testing in suspected A1AT deficiency involves quantifying serum A1AT concentration and identification of specific alleles by genotyping and phenotyping. The aim of this report was to present a case of the null allele carrier with consequent genotype/phenotype/concentration discrepancies and potential misclassification of the Z variant in a 42-year-old white man presenting with symptoms of chronic obstructive pulmonary disease (COPD). Method Serum A1AT concentration was measured using an immunoturbidimetric assay. A1AT phenotype was determined using isoelectric focusing followed with immunofixation (IEF-IF). Genotyping specifically for the S and Z allele was performed by melting curve analysis using real- time PCR and checked by an alternative PCR-RFLP method. Genotype/phenotype ambiguity and discrepancy were amended using gene sequencing. Results Laboratory testing revealed highly reduced A1AT concentration (less than 0.30 g/L), mild to moderate deficient genotype (Pi*Z allele: M/Z and Pi*S allele: M/M) and severe deficient Z homozygous phenotype (Pi ZZ). After repeated sampling, the same discordant results were verified by these tests. Further sequencing revealed two clinically relevant and defective variants: rs199422210 (a rare null allele) and rs28929474 (the Z allele). Conclusion Due to inability of genotyping kit probes to detect null/Z allele combination (which mimics the Pi ZZ phenotype), our patient was misclassified as mild to moderate deficient Pi*MZ heterozygote. In all unclear cases, whole- gene sequencing is highly recommended in order to determine definitive cause of A1AT deficiency.

α-1 antitrypsin deficiency, genotyping error, misclassification, null allele, chronic obstructive pulmonary disease, sequencing

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o izdanju

50 (3)

2019.

31583408

7

objavljeno

0007-5027

1943-7730

10.1093/labmed/lmz059

Povezanost rada

Kliničke medicinske znanosti, Farmacija

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