Alpha 1 antitrypsin deficiency
Mutations in SERPINA1 are associated with alpha-1-antitrypsin (A1AT) deficiency, which is inherited as an autosomal recessive condition. The clinical features of A1AT deficiency in the neonatal period are jaundice, pruritus, failure to thrive, and hepatosplenomegaly. In adults, A1AT deficiency results in pulmonary disease.
- Screening for Alpha-1-antitrypsin deficiency
Testing may be performed by Sanger sequencing of the entire coding regions and intron/exon boundaries of the SERPINA1 gene or by enrichment of the exons, flanking intronic and un-translated regions (5’ and 3’) of the SERPINA1 gene using TruSeq Custom Amplicon enrichment technology followed by next-generation sequencing Generation Sequencing (NGS)
The sensitivity of Sanger sequencing is over 99% for the detection of nucleotide base changes, small deletions and insertions in the regions analyzed. Mutations in regulatory regions or other untranslated regions are not detected by this test. Large deletions involving entire single exons or multiple exons, large insertions and other complex genetic events have been reported in many of these genes and will not be identified using this test methodology. Rare primer site variants may lead to erroneous results.
The predicted sensitivity of Next-Generation Sequencing is approximately 98% for the detection of nucleotide base changes or homozygous deletions in the coding exons and exon/intron boundaries of the five genes analyzed. Mutations are confirmed by targeted sequencing of the fragment(s) containing the mutation(s). Heterozygous deletions, insertions, genetic recombination events, as well as mutations in regulatory regions or other untranslated regions are not detected by this test.
If the patient has received a liver transplant or recent blood transfusion, donor DNA may be present in the blood along with patient DNA (chimerism). In this case, additional testing may be required to rule out chimerism.
How to Order
Testing for this gene is available as part of the Cholestasis panel by next-generation sequencing. Single gene sequencing, deletion/duplication analysis and familial mutation analysis are also available for this gene. Download Heritable Liver Disease requisition.
Bals, R. (2010) "Alpha-1-Antitrypsin Deficiency." Best Practice & Research. Clinical Gastroenterology 24(5): 629-33.