Identification and molecular characterization of the new alpha-1-antitrypsin deficient allele PI Y barcelona (Asp256-->Val and Pro391-->His). Mutations in brief no. 174. Online.
To characterize the molecular basis of the "new" alpha1-antitrypsin (alpha1AT) deficient variant, PI Y barcelona, DNA sequence analysis of the coding exons of the alpha1AT gene was carried out using an amplification DNA technique and direct sequencing. The PI Y barcelona allele differs from the normal M1(Val213) allele sequence by two point substitutions: a transversion of GAT TO GTT in exon III in the codon for residue 256, resulting in the amino acid change of Asp256 to Val256, and a transversion of CCC to CAC in exon V in the codon for residue 391, resulting in the amino acid substitution of Pro391 to His391. On isoelectric focusing analysis these substitutions result in a cathodal migration of the "new" variant close to the PI Z. The index case, diagnosed with severe obstructive pulmonary disease, initially phenotyped a PI ZZ, was homozygous for PI Y barcelona. The patient's serum alpha1AT level was 16 mg/dL (normal values 115-220 mg/dL). Inheritance of the PI Y barcelona was confirmed by family study. Amino acid substitution in postion 391 occurs in the C-terminal peptide region, which shows a high degree of homology with the family of serpins. Pro391 is considered to have special relevance in the secretion of alpha1AT.
Jardi
R
R
Department of Biochemistry, Hospital Universitario Valle Hebrón. Barcelona, Spain. Rjardi ar.vhebron.es
Rodriguez
F
F
Miravitlles
M
M
Vidal
R
R
Cotrina
M
M
Quer
J
J
Pascual
C
C
Weidinger
S
S
D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics*; D001224:Aspartic Acid / Q000235:genetics; D006639:Histidine / Q000235:genetics; D006801:Humans; D010641:Phenotype; D011392:Proline / Q000235:genetics; D014633:Valine / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics*
D001224:Aspartic Acid; D006639:Histidine; D011392:Proline; D014633:Valine