A new alpha 1-antitrypsin mutation, Thr-Met 85, (PI Z(bristol)) associated with novel electrophoretic properties

作者：Lovegrove JU; Jeremiah S; Gillett GT; Temple IK; Povey S; Whitehouse DB^*

来源：Annals of Human Genetics, 1997, 61(5): 385-391.

DOI：10.1046/j.1469-1809.1997.6150385.x

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 ACG (Thr) to ATG (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 NlaIII restriction endonuclease recognition site. Cell lines from two offspring tested for the presence of this NlaIII 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.

• 出版日期1997-9