title: A novel splicing mutation causes an undescribed type of analbuminemia.
abstract: Analbuminemia is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous subjects. In this report we describe a new molecular defect that caused the analbuminemic trait in a newborn of Iraqi origin. When the parents' DNA was analyzed, both subjects were found to be heterozygous for the same mutation found in the infant. All the 14 exon and flanking intron sequences of the albumin gene were amplified via PCR and screened for mutations by SSCP and heteroduplex analysis. A mutation in the DNA region encoding exon 1 and its flanking intron was revealed by the presence of a heteroduplex. The fragment, which was directly DNA sequenced, contains a previously unreported single nucleotide change, consisting in a G to A substitution at nucleotide 118 in the structural gene of the human protein. This mutation, involving the first base of intron 1, destroys the GT dinucleotide consensus sequence found at the 5' end of most intervening sequences and causes the defective pre-mRNA splicing responsible for the analbuminemic trait.
authors.affiliation: Department of Biochemistry, A. Castellani, Università di Pavia, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Campagnoli
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Lars
authors.initials: L
authors.lastname: Palmqvist
authors.forename: Anders
authors.initials: A
authors.lastname: Flisberg
authors.forename: Aimon
authors.initials: A
authors.lastname: Niklasson
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Minchotti
authors.forename: Monica
authors.initials: M
authors.lastname: Galliano
mesh_terms: D000328:Adult; D016384:Consensus Sequence; D005260:Female; D005838:Genotype; D020180:Heteroduplex Analysis; D006801:Humans; D007231:Infant, Newborn; D007493:Iraq / Q000208:ethnology; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012326:RNA Splicing; D012709:Serum Albumin / Q000172:deficiency / Q000235:genetics*; D013548:Sweden
chemical_list: D012709:Serum Albumin