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A new alpha 1‐antitrypsin mutation, Thr–Met 85, (PI Z bristol ) associated with novel electrophoretic properties
Author(s) -
LOVEGROVE J. U.,
JEREMIAH S.,
GILLETT G. T.,
TEMPLE I. K.,
POVEY S.,
WHITEHOUSE D. B.
Publication year - 1997
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1046/j.1469-1809.1997.6150385.x
Subject(s) - isoelectric focusing , gel electrophoresis , microbiology and biotechnology , mutation , biology , offspring , allele , glycosylation , genetics , pi , haptoglobin , compound heterozygosity , alpha 1 antitrypsin deficiency , biochemistry , endocrinology , enzyme , gene , immunology , pregnancy
A new AAT allele ( PI Z bristol ) has been discovered in a woman with an obstetric history of three perinatal deaths from fulminant liver disease and no living offspring. She and her father were both PI M1Z bristol heterozygotes. The Z bristol protein is active as a proteinase inhibitor but appeared to be deficient in the plasma to about the same degree as the S protein in MS heterozygotes. It focuses on the basic side of Z and lacks the normal pattern of secondary isoforms associated with the commonly occurring AAT variants and migrates faster than normal on an SDS electrophoresis gel. The Z bristol mutation was found to be a C to T transition at codon 85 changing A C G (Thr) to A T G (Met). This disrupts the N ‐glycosylation site starting at Asn 83 preventing glycosylation at residue 83 in the PI Z bristol protein and explains the protein isoelectric focusing and SDS gel electrophoresis results. An analysis of haplotypes in the propositus and her father indicated that the Z bristol mutation occurred on the common M1 ( Val 213 ) genetic background. The new mutation also led to the generation of an Nla III restriction endonuclease recognition site. Cell lines from two offspring tested for the presence of this Nla III site revealed that one had the variant and the other did not. Thus, the relationship between Z bristol and fulminant liver disease in the offspring is unclear.