title: Haemophilia B caused by a missense mutation in the prepeptide sequence of factor IX.
abstract: In the course of analysing mutation in the factor IX gene from 200 haemophilia B patients in Sweden and the UK, we have identified one patient with a prepeptide missense mutation. He has severe, antigen negative haemophilia, and complete analysis of his coding sequence reveals a single base transversion (A-->T) causing substitution of isoleucine by asparagine at position -30. This change disrupts the hydrophobic core of the prepeptide, a feature which is required for secretion. Thus, haemophilia in this patient is caused by a failure to secrete factor IX from the hepatocytes.
authors.affiliation: Paediatric Research Unit, UMDS, Guy's Hospital, London, United Kingdom.
authors.forename: P M
authors.initials: PM
authors.lastname: Green
authors.forename: V E
authors.initials: VE
authors.lastname: Mitchell
authors.forename: A
authors.initials: A
authors.lastname: McGraw
authors.forename: E
authors.initials: E
authors.lastname: Goldman
authors.forename: F
authors.initials: F
authors.lastname: Giannelli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002675:Child, Preschool; D004285:Dogs; D005164:Factor IX / Q000235:genetics*; D005260:Female; D005817:Genetic Counseling; D002836:Hemophilia B / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D011498:Protein Precursors / Q000235:genetics*; D011817:Rabbits; D017386:Sequence Homology, Amino Acid
chemical_list: D011498:Protein Precursors; D005164:Factor IX