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

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.

[1]  G. Caridi,et al.  A novel frameshift deletion in the albumin gene causes analbuminemia in a young Turkish woman. , 2010, Clinica chimica acta; international journal of clinical chemistry.

[2]  J. Andersen,et al.  FcRn binding properties of an abnormal truncated analbuminemic albumin variant. , 2010, Clinical biochemistry.

[3]  F. Chiodo,et al.  A novel frame‐shift deletion causing analbuminaemia in an Italian paediatric patient , 2010, European journal of clinical investigation.

[4]  T. Peters,et al.  Location of the mutation site in the first two reported cases of analbuminemia. , 2010, Clinical biochemistry.

[5]  R. Belostotsky,et al.  Congenital analbuminemia with acute glomerulonephritis: a diagnostic challenge , 2009, Pediatric Nephrology.

[6]  M. Galliano,et al.  Mutations and polymorphisms of the gene of the major human blood protein, serum albumin , 2008, Human mutation.

[7]  J. Andersen,et al.  A receptor-mediated mechanism to support clinical observation of altered albumin variants. , 2007, Clinical chemistry.

[8]  G. Caridi,et al.  Analbuminemia produced by a novel splicing mutation. , 2007, Clinical chemistry.

[9]  M. Galliano,et al.  Novel nonsense mutation causes analbuminemia in a Moroccan family. , 2005, Clinical chemistry.

[10]  F. Ceci,et al.  Treatment of severe hypercholesterolemia with atorvastatin in congenital analbuminemia. , 2004, The American journal of medicine.

[11]  R. Houwen,et al.  Congenital analbuminaemia: biochemical and clinical implications. A case report and literature review , 2004, European Journal of Pediatrics.

[12]  A. Lyon,et al.  Low Serum Albumin and Abnormal Body Shape in a Young Canadian First Nations Woman , 2004 .

[13]  A. Lyon,et al.  Molecular diagnosis of analbuminemia: a novel mutation identified in two Amerindian and two Turkish families. , 2002, Clinical chemistry.

[14]  A. Lyon,et al.  Influence of methodology on the detection and diagnosis of congenital analbuminemia. , 1998, Clinical chemistry.

[15]  T. Peters,et al.  All About Albumin: Biochemistry, Genetics, and Medical Applications , 1995 .

[16]  M. Galliano,et al.  A nucleotide insertion and frameshift cause analbuminemia in an Italian family. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[17]  W. Kuang,et al.  Molecular structure of the human albumin gene is revealed by nucleotide sequence within q11-22 of chromosome 4. , 1986, The Journal of biological chemistry.

[18]  P. Righetti,et al.  An improved protocol for two‐dimensional maps of serum proteins with immobilized pH gradients in the first dimension , 1985 .