A Pro----Leu substitution in codon 369 of the alpha-1-antitrypsin deficiency variant PI MHeerlen. Academic Article uri icon

Overview

MeSH

  • Blotting, Southern
  • DNA
  • Exons
  • Female
  • Humans
  • Leucine
  • Male
  • Pedigree
  • Phenotype
  • Proline
  • alpha 1-Antitrypsin Deficiency

MeSH Major

  • Codon
  • Mutation
  • RNA, Messenger
  • alpha 1-Antitrypsin

abstract

  • The molecular defect has been elucidated in the alpha-1-antitrypsin (PI) gene of a patient with a serum level of only 5 mg/100 ml and a PI M-like phenotype, designated PI MHeerlen. The restriction fragment patterns obtained by probes covering the whole gene and flanking sequences were normal, suggesting no major rearrangements. The nucleotide sequence of the exons, intron/exon junctions, and a part of the promoter region is similar to that of a PI M1(Ala213) gene except for an C----T mutation in codon 369, causing a Pro----Leu substitution. Haplotype analysis and oligonucleotide hybridization studies demonstrated the homozygous state of the mutation in the index case. It is most likely that the Pro369----Leu substitution is responsible for the low serum alpha-1-antitrypsin concentration of the patient because this mutation is solely confined to the PI MHeerlen allele and no other relevant mutations could be revealed. As proline is important for the secondary and tertiary structure of proteins, the mutation may cause an abnormal processing of the nascent polypeptide. The same mutation was observed in two unrelated subjects known to carry a PI allele giving a low serum alpha-1-antitrypsin level.

publication date

  • February 1989

has subject area

  • Blotting, Southern
  • Codon
  • DNA
  • Exons
  • Female
  • Humans
  • Leucine
  • Male
  • Mutation
  • Pedigree
  • Phenotype
  • Proline
  • RNA, Messenger
  • alpha 1-Antitrypsin
  • alpha 1-Antitrypsin Deficiency

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 2784123

Additional Document Info

start page

  • 264

end page

  • 268

volume

  • 81

number

  • 3