title: Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene.
abstract: BACKGROUND
  Congenital analbuminemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. It is an allelic heterogeneous defect, caused by variety of mutations within the albumin gene in homozygous or compound heterozygous state. Herein we report the clinical and molecular characterization of a new case of congenital analbuminemia diagnosed in a female newborn of consanguineous (first degree cousins) parents from Ankara, Turkey, who presented with a low albumin concentration (< 8 g/L) and severe clinical symptoms.
  
  
  METHODS
  The albumin gene of the index case was screened by single-strand conformation polymorphism, heteroduplex analysis, and direct DNA sequencing. The effect of the splicing mutation was evaluated by examining the cDNA obtained by reverse transcriptase - polymerase chain reaction (RT-PCR) from the albumin mRNA extracted from proband's leukocytes.
  
  
  RESULTS
  DNA sequencing revealed that the proband is homozygous, and both parents are heterozygous, for a novel G>A transition at position c.1652+1, the first base of intron 12, which inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. The splicing defect results in the complete skipping of the preceding exon (exon 12) and in a frame-shift within exon 13 with a premature stop codon after the translation of three mutant amino acid residues.
  
  
  CONCLUSIONS
  Our results confirm the clinical diagnosis of congenital analbuminemia in the proband and the inheritance of the trait and contribute to shed light on the molecular genetics of analbuminemia.
authors.affiliation: Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini IRCCS, Genova, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.affiliation: Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini IRCCS, Genova, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Dagnino
authors.affiliation: Ankara University School of Medicine, Department of Pediatrics, Division of Neonatology, Ankara, Turkey.
authors.forename: Omer
authors.initials: O
authors.lastname: Erdeve
authors.affiliation: Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini IRCCS, Genova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Di Duca
authors.affiliation: Ankara University School of Medicine, Department of Pediatrics, Division of Neonatology, Ankara, Turkey.
authors.forename: Duran
authors.initials: D
authors.lastname: Yildiz
authors.affiliation: Ankara University School of Medicine, Department of Pediatrics, Division of Neonatology, Ankara, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Alan
authors.affiliation: Ankara University School of Medicine, Department of Pediatrics, Division of Neonatology, Ankara, Turkey.
authors.forename: Begum
authors.initials: B
authors.lastname: Atasay
authors.affiliation: Ankara University School of Medicine, Department of Pediatrics, Division of Neonatology, Ankara, Turkey.
authors.forename: Saadet
authors.initials: S
authors.lastname: Arsan
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Campagnoli
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Galliano
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Minchiotti
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D020180:Heteroduplex Analysis; D006801:Humans; D034141:Hypoalbuminemia / Q000151:congenital* / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D012709:Serum Albumin / Q000172:deficiency / Q000235:genetics*; D000075462:Serum Albumin, Human; D055815:Young Adult
chemical_list: C422455:ALB protein, human; D012709:Serum Albumin; D000075462:Serum Albumin, Human
keywords: DNA and cDNA sequence analysis; albumin gene; congenital analbuminemia; human serum albumin; splicing mutation