Emphysema associated with complete absence of α1-antitrypsin of a stop codon in a n α1-antitrypsin-coding exon

K. Satoh, T. Nukiwa, M. Brantly, R. I. Garver, M. Hofker, M. Courtney, R. G. Crystal

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Homozygous inheritance of the null bellingham α1-antitrypsin (α1AT) gene is associated with early-onset emphysema, resulting from the lack of α1AT to protect the lung from neutrophil elastase. Cloning and sequencing of the null bellingham gene demonstrated that the promoter region, coding exons, and all exon-intron junctions were normal except for a single base substitution in exon III, causing the normal lys217 (AAG) to become a stop codon (TAG). Evaluation of genomic DNA of family members by using oligonucleotides directed toward this region demonstrated that the index case had inherited this mutation in a homozygous fashion. Although the consequences to the individual (i.e., emphysema) are identical to those associated with the common homozygous Z mutation, the homozygous null bellingham form of α1AT deficiency has a very different genetic basis.

Original languageEnglish
Pages (from-to)77-83
Number of pages7
JournalAmerican Journal of Human Genetics
Volume42
Issue number1
Publication statusPublished - 1 Jan 1988
Externally publishedYes

Fingerprint

Terminator Codon
Emphysema
Exons
Leukocyte Elastase
Mutation
Genetic Promoter Regions
Oligonucleotides
Introns
Genes
Organism Cloning
Lung
DNA

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Emphysema associated with complete absence of α1-antitrypsin of a stop codon in a n α1-antitrypsin-coding exon. / Satoh, K.; Nukiwa, T.; Brantly, M.; Garver, R. I.; Hofker, M.; Courtney, M.; Crystal, R. G.

In: American Journal of Human Genetics, Vol. 42, No. 1, 01.01.1988, p. 77-83.

Research output: Contribution to journalArticle

Satoh, K. ; Nukiwa, T. ; Brantly, M. ; Garver, R. I. ; Hofker, M. ; Courtney, M. ; Crystal, R. G. / Emphysema associated with complete absence of α1-antitrypsin of a stop codon in a n α1-antitrypsin-coding exon. In: American Journal of Human Genetics. 1988 ; Vol. 42, No. 1. pp. 77-83.
@article{d2b68b49c8ca4c609c380ce03ca5a868,
title = "Emphysema associated with complete absence of α1-antitrypsin of a stop codon in a n α1-antitrypsin-coding exon",
abstract = "Homozygous inheritance of the null bellingham α1-antitrypsin (α1AT) gene is associated with early-onset emphysema, resulting from the lack of α1AT to protect the lung from neutrophil elastase. Cloning and sequencing of the null bellingham gene demonstrated that the promoter region, coding exons, and all exon-intron junctions were normal except for a single base substitution in exon III, causing the normal lys217 (AAG) to become a stop codon (TAG). Evaluation of genomic DNA of family members by using oligonucleotides directed toward this region demonstrated that the index case had inherited this mutation in a homozygous fashion. Although the consequences to the individual (i.e., emphysema) are identical to those associated with the common homozygous Z mutation, the homozygous null bellingham form of α1AT deficiency has a very different genetic basis.",
author = "K. Satoh and T. Nukiwa and M. Brantly and Garver, {R. I.} and M. Hofker and M. Courtney and Crystal, {R. G.}",
year = "1988",
month = "1",
day = "1",
language = "English",
volume = "42",
pages = "77--83",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Emphysema associated with complete absence of α1-antitrypsin of a stop codon in a n α1-antitrypsin-coding exon

AU - Satoh, K.

AU - Nukiwa, T.

AU - Brantly, M.

AU - Garver, R. I.

AU - Hofker, M.

AU - Courtney, M.

AU - Crystal, R. G.

PY - 1988/1/1

Y1 - 1988/1/1

N2 - Homozygous inheritance of the null bellingham α1-antitrypsin (α1AT) gene is associated with early-onset emphysema, resulting from the lack of α1AT to protect the lung from neutrophil elastase. Cloning and sequencing of the null bellingham gene demonstrated that the promoter region, coding exons, and all exon-intron junctions were normal except for a single base substitution in exon III, causing the normal lys217 (AAG) to become a stop codon (TAG). Evaluation of genomic DNA of family members by using oligonucleotides directed toward this region demonstrated that the index case had inherited this mutation in a homozygous fashion. Although the consequences to the individual (i.e., emphysema) are identical to those associated with the common homozygous Z mutation, the homozygous null bellingham form of α1AT deficiency has a very different genetic basis.

AB - Homozygous inheritance of the null bellingham α1-antitrypsin (α1AT) gene is associated with early-onset emphysema, resulting from the lack of α1AT to protect the lung from neutrophil elastase. Cloning and sequencing of the null bellingham gene demonstrated that the promoter region, coding exons, and all exon-intron junctions were normal except for a single base substitution in exon III, causing the normal lys217 (AAG) to become a stop codon (TAG). Evaluation of genomic DNA of family members by using oligonucleotides directed toward this region demonstrated that the index case had inherited this mutation in a homozygous fashion. Although the consequences to the individual (i.e., emphysema) are identical to those associated with the common homozygous Z mutation, the homozygous null bellingham form of α1AT deficiency has a very different genetic basis.

UR - http://www.scopus.com/inward/record.url?scp=0023877411&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023877411&partnerID=8YFLogxK

M3 - Article

C2 - 3257351

AN - SCOPUS:0023877411

VL - 42

SP - 77

EP - 83

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 1

ER -