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

Gianluca Caridi, Monica Dagnino, Omer Erdeve, Marco Di Duca, Duran Yildiz, Serdar Alan, Begum Atasay, Saadet Arsan, Monica Campagnoli, Monica Galliano, Lorenzo Minchiotti

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 newborn 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.

Original languageEnglish
Pages (from-to)151-158
Number of pages8
JournalBiochemia Medica
Volume24
Issue number1
DOIs
Publication statusPublished - 2014

Fingerprint

Albumins
Exons
Genes
Introns
Defects
RNA Splice Sites
Nonsense Codon
Consensus Sequence
Turkey
Serum Albumin
Molecular Biology
Amino Acids
Mutation
Genetics

Keywords

  • Albumin gene
  • Congenital analbuminemia
  • DNA and cDNA sequence analysis
  • Human serum albumin
  • Splicing mutation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Caridi, G., Dagnino, M., Erdeve, O., Di Duca, M., Yildiz, D., Alan, S., ... Minchiotti, L. (2014). Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene. Biochemia Medica, 24(1), 151-158. https://doi.org/10.11613/BM.2014.017

Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene. / Caridi, Gianluca; Dagnino, Monica; Erdeve, Omer; Di Duca, Marco; Yildiz, Duran; Alan, Serdar; Atasay, Begum; Arsan, Saadet; Campagnoli, Monica; Galliano, Monica; Minchiotti, Lorenzo.

In: Biochemia Medica, Vol. 24, No. 1, 2014, p. 151-158.

Research output: Contribution to journalArticle

Caridi, G, Dagnino, M, Erdeve, O, Di Duca, M, Yildiz, D, Alan, S, Atasay, B, Arsan, S, Campagnoli, M, Galliano, M & Minchiotti, L 2014, 'Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene', Biochemia Medica, vol. 24, no. 1, pp. 151-158. https://doi.org/10.11613/BM.2014.017
Caridi, Gianluca ; Dagnino, Monica ; Erdeve, Omer ; Di Duca, Marco ; Yildiz, Duran ; Alan, Serdar ; Atasay, Begum ; Arsan, Saadet ; Campagnoli, Monica ; Galliano, Monica ; Minchiotti, Lorenzo. / Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene. In: Biochemia Medica. 2014 ; Vol. 24, No. 1. pp. 151-158.
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AU - Yildiz, Duran

AU - Alan, Serdar

AU - Atasay, Begum

AU - Arsan, Saadet

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AU - Galliano, Monica

AU - Minchiotti, Lorenzo

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N2 - 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 newborn 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.

AB - 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 newborn 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.

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