title: Congenital analbuminaemia: molecular defects and biochemical and clinical aspects.
abstract: BACKGROUND
  DNA and mRNA sequencing of the coding regions of the human albumin gene (ALB) and of its intron/exon junctions has revealed twenty-one different molecular defects causing congenital analbuminaemia (CAA).
  
  
  METHODS
  To describe the mutations in molecular terms and to present the current knowledge about the most important biochemical and clinical effects of CAA.
  
  
  CONCLUSIONS
  CAA is rare, but its frequency seems to be significantly higher in restricted and minimally admixed populations. The condition affects especially the lipid metabolism but apart from a possible increased risk for atherosclerotic complications, it is generally associated with mild clinical symptoms in adults. By contrast, several reports indicate that analbuminaemic individuals may be at risk during the perinatal and childhood periods, in which they seem to show increased morbidity and mortality. The twenty-one causative defects include seven nonsense mutations, seven changes affecting splicing, five frame-shift/deletions, one frame-shift/insertion and one mutation in the start codon. These results indicate that the trait is an allelic heterogeneous disorder caused by homozygous (nineteen cases) or compound heterozygous (single case) inheritance of defects. Most mutations are unique, but one, named Kayseri, is responsible for about half of the known cases.
  
  
  CONCLUSIONS
  Study of the defects in the ALB resulting in CAA allows the identification of "hot spot" regions and contributes to understanding the molecular mechanism underlying the trait. Such studies could also give molecular information about different aspects of ALB regulation and shed light on the regulatory mechanisms involved in the synthesis of the protein. This article is part of a Special Issue entitled Serum Albumin.
authors.affiliation: Department of Molecular Medicine, University of Pavia, I-27100 Pavia, Italy. Electronic address: loremin@unipv.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Minchiotti
authors.forename: Monica
authors.initials: M
authors.lastname: Galliano
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kragh-Hansen
authors.forename: Theodore
authors.initials: T
authors.lastname: Peters
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D012709:Serum Albumin / Q000172:deficiency*
chemical_list: D012709:Serum Albumin
keywords: Albumin gene; Clinical effects; Congenital analbuminaemia; Gene sequence; Molecular diagnosis; Mutations