title: A novel splicing mutation in the albumin gene (c.270+1G>T) causes analbuminaemia in a German infant.
abstract: Congenital analbuminaemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. The clinical diagnosis may be challenging because of the absence of unambiguous symptoms and because hypoalbuminemia may have many causes different from a genetic lack of the protein. We describe the clinical and molecular characterization of a new case of congenital analbuminaemia in an infant of apparently non-consanguineous parents from Treves, Germany. For molecular diagnosis, we used our strategy, based on the screening of the albumin gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing, which revealed that the proband is homozygous and both parents are heterozygous, for a novel G > T transversion at nucleotide c.270+ 1, the first base of intron 3. The mutation inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. In conclusion, we report the clinical findings and the molecular defect of this case, which contributes to a better understanding of the biological mechanism of congenital analbuminaemia.
authors.affiliation: Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini IRCCS, Genova, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.affiliation: Department of Pediatrics, Klinikum Mutterhaus der Borromaeerinnen, Trier, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Thomas
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Campagnoli
authors.affiliation: Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini IRCCS, Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lugani
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 loremin@unipv.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Minchiotti
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D005858:Germany; D006801:Humans; D034141:Hypoalbuminemia / Q000235:genetics*; D008297:Male; D017354:Point Mutation; D022821:RNA Splice Sites; D012709:Serum Albumin / Q000235:genetics*
chemical_list: D022821:RNA Splice Sites; D012709:Serum Albumin
keywords: DNA sequence analysis; Human serum albumin; albumin gene; congenital analbuminaemia; splicing mutation