Molecular Diagnosis of Analbuminemia: A New Case Caused by a Nonsense Mutation in the Albumin Gene

Monica Dagnino,Fabienne Aregger,Monica Galliano,Lorenzo Minchiotti,Gianluca Caridi,Monica Campagnoli,Adrian Duss,Ueli Haenni

doi:10.3390/ijms12117314

Abstract

Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin (ALB). We report here a new case diagnosed in a 45 years old man of Southwestern Asian origin, living in Switzerland, on the basis of his low ALB concentration (0.9 g/L) in the absence of renal or gastrointestinal protein loss, or liver dysfunction. The clinical diagnosis was confirmed by a mutational analysis of the albumin (ALB) gene, carried out by single-strand conformational polymorphism (SSCP), heteroduplex analysis (HA), and DNA sequencing. This screening of the ALB gene revealed that the proband is homozygous for two mutations: the insertion of a T in a stretch of eight Ts spanning positions c.1289 + 23–c.1289 + 30 of intron 10 and a c.802 G > T transversion in exon 7. Whereas the presence of an additional T in the poly-T tract has no direct deleterious effect, the latter nonsense mutation changes the codon GAA for Glu244 to the stop codon TAA, resulting in a premature termination of the polypeptide chain. The putative protein product would have a length of only 243 amino acid residues instead of the normal 585 found in the mature serum albumin, but no evidence for the presence in serum of such a truncated polypeptide chain could be obtained by two dimensional electrophoresis and western blotting analysis.

Highlights

Congenital analbuminemia (MIM 103600) is a very rare autosomal recessive disorder [1]
In our continuing study of this defect, we report here a new case of analbuminemia observed in a 45-year-old man of Lebanese origin living in Switzerland and the identification of the causative mutation within the ALB gene
The results show that analbuminemia is an allelic heterogeneous disorder caused by homozygous or compound heterozygous inheritance of defects

Summary

Introduction

Congenital analbuminemia (MIM 103600) is a very rare autosomal recessive disorder [1]. Fetal or neonatal death of siblings was frequently observed in the families of analbuminemic subjects [2,3] This seems to confirm the hypothesis that only a few analbuminemic individuals survive past the neonatal state and that serum albumin (ALB) may play a crucial role in fetal development [4]. The finding of a low ALB concentration during routine serum electrophoresis, with normal liver function and no gastrointestinal or renal protein loss, suggests the clinical diagnosis. This needs to be confirmed by the molecular diagnosis, based on the identification of the causative mutation within the albumin (ALB) gene by DNA sequence analysis. In our continuing study of this defect, we report here a new case of analbuminemia observed in a 45-year-old man of Lebanese origin living in Switzerland and the identification of the causative mutation within the ALB gene

Patient

Mutational Analysis

Immunoblotting

Two-Dimensional Electrophoresis

Conclusions