title: Molecular characterization of a new alpha-1-antitrypsin M variant allele, Mwhitstable: implications for DNA-based diagnosis.
abstract: The mother and second child from a family, already with one PI ZZ child, were typed PI MZ by isoelectric focusing and unexpectedly as PI ZZ using a commercial alpha-1-antitrypsin genotyping kit. Both methods typed the father and first child as PI MZ and PI ZZ, respectively. DNA sequence analysis identified a 26-base pair (bp) deletion and 2-bp insertion in intron IV of the normal PI*M allele from both the mother and second child. The majority of the binding site for an amplification primer of the genotyping kit was absent in the variant deletion-insertion allele. The apparent PI*Z/PI*Z genotype of the mother and second child therefore arose from amplification of the PI*Z allele alone. Two hundred random DNA samples were subsequently examined and 5 of these were found to be heterozygous for the same deletion-insertion allele. The authors have designated the previously undescribed PI*M allele that harbors this benign polymorphism PI*Mwhitstable. The genotyping kit has been redesigned and revalidated, and its performance is not affected by the presence of the PI*Mwhitstable allele. The Gen Bank accession number for the nucleotide sequence described is AF159454.
authors.affiliation: AstraZeneca Diagnostics, Northwich, Cheshire, UK.
authors.forename: H J
authors.initials: HJ
authors.lastname: Ambrose
authors.forename: S M
authors.initials: SM
authors.lastname: Chambers
authors.forename: G
authors.initials: G
authors.lastname: Mieli-Vergani
authors.forename: R
authors.initials: R
authors.lastname: Ferrie
authors.forename: C R
authors.initials: CR
authors.lastname: Newton
authors.forename: N H
authors.initials: NH
authors.lastname: Robertson
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000032:analysis / Q000302:isolation & purification; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010641:Phenotype; D011110:Polymorphism, Genetic; D015183:Restriction Mapping; D020080:Tandem Repeat Sequences; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D000515:alpha 1-Antitrypsin; D004247:DNA