The Department of Genetic Medicine at Weill Cornell leads a dynamic and innovative translational research program, advancing diverse fields such as Genetic Therapy and Personalized Medicine.
Our translational research program aims to leverage our expertise in genetic therapies and personalized medicine to develop clinical solutions that target the molecular causes of human diseases.
The Department of Genetic Medicine advances treatments and diagnostics through diverse clinical trials, including drug testing and research to better understand diseases.
The Department of Genetic Medicine at Weill Cornell leads a dynamic and innovative translational research program, advancing diverse fields such as Genetic Therapy and Personalized Medicine.
Our translational research program aims to leverage our expertise in genetic therapies and personalized medicine to develop clinical solutions that target the molecular causes of human diseases.
The Department of Genetic Medicine advances treatments and diagnostics through diverse clinical trials, including drug testing and research to better understand diseases.
Characterization of the intracellular mechanism causing the alpha-1-antitrypsin Nullgranite falls deficiency state.
Publication Type
Academic Article
Authors
Holmes M, Curiel D, Brantly M, Crystal R
Journal
Am Rev Respir Dis
Volume
140
Issue
6
Pagination
1662-7
Date Published
12/01/1989
ISSN
0003-0805
Keywords
alpha 1-Antitrypsin Deficiency
Abstract
The alpha-1-antitrypsin (alpha 1AT) Null alleles are those for which no alpha 1AT can be detected in the serum attributable to the gene. The intracellular consequences of the various substitution, deletion, and insertion mutations causing the Null state can be categorized into two groups: those associated with detectable alpha 1AT mRNA transcripts and those with no detectable alpha 1AT mRNA transcripts. To classify the intracellular mechanism associated with the Nullgranite falls allele (Tyr160 TAC, C deletion, 5' frameshift----Stop160 TAG), a Nullgranite falls homozygote was evaluated. Genotypic diagnosis of the Nullgranite falls homozygous state was determined using the polymerase chain reaction and Nullgranite falls specific primers. Total cellular RNA extracted from alveolar macrophages of the index case was compared to that from a normal M1 homozygote for the presence of alpha 1AT mRNA transcripts using Northern blot analysis and hybridization to either a 32P-labeled full length alpha 1AT cDNA probe or (as a control) a 32P-labeled gamma-actin cDNA probe. Although the macrophages of both the Nullgranite falls homozygote and the normal showed gamma-actin mRNA transcripts in comparable amounts, Nullgranite falls macrophages contained no detectable alpha 1AT mRNA transcripts whereas the normal had the expected 1.8 kb alpha 1AT mRNA transcripts. Thus, the Nullgranite falls allele can be classified along with Nullbellingham as a Null allele associated with no detectable alpha 1AT mRNA. These observations highlight the marked heterogeneity in the molecular processes causing the Null state, despite an identical phenotype at the clinical level.