SERPINA1 Full-Gene Sequencing Identifies Rare Mutations Not Detected in Targeted Mutation Analysis.

Autor:	Graham RP; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Dina MA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Howe SC; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Butz ML; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Willkomm KS; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Murray DL; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Snyder MR; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Rumilla KM; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota., Halling KC; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Highsmith WE Jr; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota. Electronic address: highsmith.w@mayo.edu.
Jazyk:	angličtina
Zdroj:	The Journal of molecular diagnostics : JMD [J Mol Diagn] 2015 Nov; Vol. 17 (6), pp. 689-94. Date of Electronic Publication: 2015 Aug 28.
DOI:	10.1016/j.jmoldx.2015.07.002
Abstrakt:	Genetic α-1 antitrypsin (AAT) deficiency is characterized by low serum AAT levels and the identification of causal mutations or an abnormal protein. It needs to be distinguished from deficiency because of nongenetic causes, and diagnostic delay may contribute to worse patient outcome. Current routine clinical testing assesses for only the most common mutations. We wanted to determine the proportion of unexplained cases of AAT deficiency that harbor causal mutations not identified through current standard allele-specific genotyping and isoelectric focusing (IEF). All prospective cases from December 1, 2013, to October 1, 2014, with a low serum AAT level not explained by allele-specific genotyping and IEF were assessed through full-gene sequencing with a direct sequencing method for pathogenic mutations. We reviewed the results using American Council of Medical Genetics criteria. Of 3523 cases, 42 (1.2%) met study inclusion criteria. Pathogenic or likely pathogenic mutations not identified through clinical testing were detected through full-gene sequencing in 16 (38%) of the 42 cases. Rare mutations not detected with current allele-specific testing and IEF underlie a substantial proportion of genetic AAT deficiency. Full-gene sequencing, therefore, has the ability to improve accuracy in the diagnosis of AAT deficiency. (Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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