title: A nucleotide deletion and frame-shift cause analbuminemia in a Turkish family.
abstract: Congenital analbuminemia is an autosomal recessive disorder, in which albumin, the major blood protein, is present only in a minute amount. The condition is a rare allelic heterogeneous defect, only about seventy cases have been reported worldwide. To date, more than twenty different mutations within the albumin gene have been found to cause the trait. In our continuing study of the molecular genetics of congenital analbuminemia, we report here the clinical and biochemical findings and the mutation analysis of the gene in two Turkish infants. For the molecular analysis, we used our strategy, based on the screening of the gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing. The results showed that both patients are homozygous for the deletion of a cytosine residue in exon 5, in a stretch of four cytosines starting from nucleotide position 524 and ending at position 527 (NM_000477.5(ALB):c.527delC). The subsequent frame-shift inserts a stop codon in position 215, markedly reducing the size of the predicted protein product. The parents are both heterozygous for the same mutation, for which we propose the name Erzurum from the city of origin of the family. In conclusion, our results show that in this family congenital analbuminemia is caused by a novel frame-shift/deletion defect, confirm the inheritance of the trait, and contribute to advance our understanding of the molecular basis underlying this condition.
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 Medical Genetics, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey.
authors.forename: Elif Yilmaz
authors.initials: EY
authors.lastname: Gulec
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 Pediatric Metabolism and Nutrition, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Onal
authors.affiliation: Department of Biochemistry, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey.
authors.forename: Duzgun
authors.initials: D
authors.lastname: Kilic
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: D000328:Adult; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D020180:Heteroduplex Analysis; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D017384:Sequence Deletion / Q000235:genetics*; D012709:Serum Albumin / Q000172:deficiency* / Q000235:genetics*; D014421:Turkey
chemical_list: D012709:Serum Albumin
keywords: DNA mutational analysis; congenital analbuminemia; frame-shift; single base deletion