Emphysema associated with complete absence of alpha 1- antitrypsin in serum and the homozygous inheritance [corrected] of a stop codon in an alpha 1-antitrypsin-coding exon.

Publication Type	Case Report
Authors	Satoh K, Nukiwa T, Brantly M, Garver R, Hofker M, Courtney M, Crystal R
Journal	Am J Hum Genet
Volume	42
Issue	1
Pagination	77-83
Date Published	01/01/1988
ISSN	0002-9297
Keywords	Codon, Exons, Pulmonary Emphysema, RNA, Messenger, alpha 1-Antitrypsin Deficiency
Abstract	Homozygous inheritance of the null bellingham alpha 1-antitrypsin (alpha 1AT) gene is associated with early-onset emphysema, resulting from the lack of alpha 1AT 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 alpha 1AT deficiency has a very different genetic basis.
PubMed ID	3257351
PubMed Central ID	PMC1715304