For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
23
views
9
references
 Top references
cited by
3
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      95
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A challenging diagnosis of alpha-1-antitrypsin deficiency: identification of a patient with a novel F/Null phenotype

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Alpha-1-antitrypsin (A1AT) deficiency is a genetic disease characterized by low levels and/or function of A1AT protein. A1AT deficiency can result in the development of COPD, liver disease, and certain skin conditions. The disease can be diagnosed by demonstrating a low level of A1AT protein and genotype screening for S and Z mutations, which are the most common. However, there are many genetic variants in A1AT deficiency, and this screening may miss rarer cases, such as those caused by dysfunctional protein. We identified a patient with a previously unreported F/null phenotype that was missed by routine screening. This case highlights the wide variation in possible mutations, limitations in diagnostics, and the importance of combining clinical suspicion with measurement of protein levels, phenotypic analysis, and in appropriate cases expanded genetic analysis.

          Related collections

          Most cited references9

          • Record: found
          • Abstract: not found
          • Article: not found

          Clinical practice. Alpha1-antitrypsin deficiency.

          Robert Sandhaus, E Silverman (2009)
          Article 0 comments Cited 106 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Worldwide racial and ethnic distribution of alpha1-antitrypsin deficiency: summary of an analysis of published genetic epidemiologic surveys.

            F Serres (2002)
            Alpha1-antitrypsin (AAT) deficiency is a genetic disease that is widely known in Europe as a disease of white individuals, who, along with their descendants in other parts of the world, are at the highest risk for liver and/or lung disease. There is a limited database of individuals affected by this disease worldwide. It has been estimated, for example, that there are 70,000 to 100,00 individuals affected in the United States, with comparable numbers in Europe. Genetic epidemiologic studies in the peer-reviewed literature have been used in an exploratory study to estimate the number of carriers and the number of those individuals who are homozygous or heterozygous for the two most common defective alleles for AAT deficiency in 58 individual countries. The total country database of 373 control cohorts has been combined to estimate the numbers of carriers and deficiency allele combinations for PiS and PiZ in 11 geographic regions and worldwide. The study was designed to be illustrative rather than comprehensive, and more detailed publication of the enormous database developed in this exploratory study is planned. The database presented indicates that in a total population of 4.4 billion in the countries surveyed worldwide, there are at least 116 million carriers (PiMS and PiMZ) and 3.4 million deficiency allele combinations (PiSS, PiSZ, and PiZZ). Furthermore, this database demonstrates that AAT deficiency is found in various populations of African blacks, Arabs and Jews in the Middle East, whites in Australia/New Zealand, Europe, and North America, central Asians, far east Asians, and southeast Asians. These data demonstrate that AAT deficiency is not just a disease of whites in Europe, but that it affects individuals in all racial subgroups worldwide. In addition, AAT deficiency may be one of the most common serious hereditary disorders in the world.
            Article 0 comments Cited 55 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Alpha-1 antitrypsin Null mutations and severity of emphysema.

              Rune Frants, Jan Stolk, B Veldhuisen … (2008)
              Alpha-1 antitrypsin (AAT) deficiency is an autosomal-codominant disorder, caused by mutations in the SERPINA1 gene on chromosome 14. Individuals affected by the most common mutations, SZ and ZZ, have serum AAT concentrations of 25% and 15% of normal levels, and present a higher risk of emphysema. Mutations causing total absence of serum AAT (Null mutations) were suggested to be associated with very early onset emphysema but their clinical phenotype is poorly known. Absence of AAT in Null mutations results in more severe emphysema as compared to ZZ and SZ. We genotyped all known Dutch subjects (n=12) with absent serum AAT, and compared their lung function values (FEV1 and KCO) with those of individuals with ZZ and SZ genotype, matched for age and smoking history. All subjects with absent serum AAT presented homozygous Null mutations. In three subjects, a new mutation in exon 2 of the SERPINA1 gene was found. Subjects with Null mutations showed significantly lower lung function values than SZ and ZZ individuals (p=0.000 and 0.001 for FEV1 and KCO, respectively). In all groups, there was a positive correlation between serum AAT and lung function values (p=0.025 and 0.014 for FEV1 and KCO, respectively). Serum levels of AAT are correlated with the severity of pulmonary phenotype. Subjects with Null mutations should be considered a subgroup at particularly high risk of emphysema within AAT deficiency (AATD). Early detection of carriers of this genotype would be important for preventive and therapeutic interventions.
              Article 0 comments Cited 33 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Allergy Asthma Clin Immunol
                Title: Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology
                Publisher: BioMed Central
                ISSN (Print): 1710-1484
                ISSN (Electronic): 1710-1492
                Publication date Collection: 2011
                Publication date (Electronic): 13 November 2011
                Volume: 7
                Issue: 1
                Page: 18
                Affiliations
                [1 ]Department of Medicine, Section of Allergy and Immunology, The Pennsylvania State University Milton S. Hershey Medical Center, 500 University Dr., Hershey, PA 17033, USA
                [2 ]Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Dr., Hershey, PA 17033, USA
                [3 ]Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Hilton 2-10D, 200 First St. SW, Rochester, MN, 55905, USA
                Article
                Publisher ID: 1710-1492-7-18
                DOI: 10.1186/1710-1492-7-18
                PMC ID: 3229436
                PubMed ID: 22078084
                SO-VID: 1e02b72b-3828-4771-ad4e-2cb23eb04333
                Copyright © Copyright ©2011 Ringenbach et al; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 28 September 2011
                Date accepted : 13 November 2011
                Categories
                Subject: Case Report

                ScienceOpen disciplines: Immunology
                Keywords: genotype,diagnostic testing,phenotype,alpha-1-antitrypsin
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: genotype, diagnostic testing, phenotype, alpha-1-antitrypsin

                Comments

                Comment on this article

                scite_

                Similar content95

                See all similar

                Cited by3

                See all cited by

                Most referenced authors135

                See all reference authors