title: Alpha1-antitrypsin Pittsburgh in a family with bleeding tendency.
abstract: We describe a 16-year-old girl and her 41-year-old father who both had a bleeding tendency, dramatic prolongation of all standard clotting assays, undetectable levels of plasma protein C activity, and low or borderline levels of factors X, XI and XII. Plasma and serum electrophoresis revealed a minor peak following the main alpha(1) globulin peak, of which the proportion was increased. Platelet aggregation by thrombin (final concentration 1 U/mL) was absent in both patients, but this inhibition can be overcome by increasing the concentration of thrombin (4 U/mL). The molecular defect responsible for these coagulation abnormalities was identified by genomic sequencing. Both patients are heterozygous for alpha(1)-antitrypsin Met 358 to Arg (alpha(1)-antitrypsin Pittsburgh). Seven other members of this pedigree had normal coagulation tests and do not carry the same genetic mutation. This unique family with alpha1-antitrypsin Pittsburgh sheds some light on the study of this extremely rare mutation and its inheritance.
authors.affiliation: 1Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China.
authors.forename: Baolai
authors.initials: B
authors.lastname: Hua
authors.forename: Liankai
authors.initials: L
authors.lastname: Fan
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Edward G D
authors.initials: EG
authors.lastname: Tuddenham
mesh_terms: D000293:Adolescent; D000328:Adult; D001780:Blood Coagulation Tests; D001797:Blood Protein Electrophoresis; D004252:DNA Mutational Analysis; D005170:Factor X / Q000378:metabolism; D005172:Factor XI / Q000378:metabolism; D005174:Factor XII / Q000378:metabolism; D005192:Family Health; D005260:Female; D006474:Hemorrhagic Disorders / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D000515:alpha 1-Antitrypsin / Q000235:genetics*
chemical_list: D000515:alpha 1-Antitrypsin; C038915:alpha 1-antitrypsin Pittsburgh; D005170:Factor X; D005174:Factor XII; D005172:Factor XI