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

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 homozigous or compound heteroziguos state. We report here 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 level (<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–PCR (RT-PCR) from the albumin mRNA extracted from proband’s leukocytes. Results DNA sequencing revealed that the proband is homozygous, and both parents 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.