Pregledni rad

https://doi.org/10.11613/BM.2014.017

Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene

Gianluca Caridi ; Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini IRCCS, Genova, Italy
Monica Dagnino ; Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini IRCCS, Genova, Italy
Omer Erdeve ; Ankara University School of Medicine, Department of Pediatrics, Division of Neonatology, Ankara, Turkey
Marco Di Duca ; Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini IRCCS, Genova, Italy
Duran Yildiz ; Ankara University School of Medicine, Department of Pediatrics, Division of Neonatology, Ankara, Turkey
Serdar Alan ; Ankara University School of Medicine, Department of Pediatrics, Division of Neonatology, Ankara, Turkey
Begum Atasay ; Ankara University School of Medicine, Department of Pediatrics, Division of Neonatology, Ankara, Turkey
Saadet Arsan ; Ankara University School of Medicine, Department of Pediatrics, Division of Neonatology, Ankara, Turkey
Monica Campagnoli ; Department of Molecular Medicine, University of Pavia, Pavia, Italy
Monica Galliano ; Department of Molecular Medicine, University of Pavia, Pavia, Italy
Lorenzo Minchiotti orcid.org/0000-0002-7043-482X ; Department of Molecular Medicine, University of Pavia, Pavia, Italy

Sažetak

Introduction: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 new-born of consanguineous (first degree cousins) parents from Ankara, Turkey, who presented with a low albumin concentration (< 8 g/L) and severe clinical symptoms.
Materials and 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.

Ključne riječi

human serum albumin; albumin gene; congenital analbuminemia; DNA and cDNA sequence analysis; splicing mutation

Hrčak ID:

115758

URI

https://hrcak.srce.hr/115758

Datum izdavanja:

15.2.2014.

Posjeta: 1.060 *