Analbuminemia in a Slovak Romany (gypsy) family: case report and mutational analysis.

Abstract Background Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin. Here we report three new cases of hereditary analbuminemia, fortuitously detected in three Slovak Romany children, members of the same family, and define the molecular defect that causes the analbuminemic trait. Methods Total DNA, extracted from peripheral blood samples from six members of the family, was PCR-amplified using oligonucleotide primers designed to amplify the 14 exons of the human albumin gene and the flanking intron regions. The products were screened for mutations by single-strand conformation polymorphism (SSCP) and heteroduplex analyses (HA). HA allowed the identification of the abnormal fragment, which was then sequenced. Results In the 3 patients the analbuminemic trait was caused by the same mutation, an AT deletion at nucleotides 2430–31, the 91th and 92th bases of exon 3. This defect, previously identified as Kayseri mutation [Galliano, M. Campagnoli, M, Rossi A, Wirsing von Konig CH, Lyon AW, Cefle K, et al. Molecular diagnosis of analbuminemia: a novel mutation identified in two Amerindian and two Turkish families. Clin Chem 2002;48: 844–9.], produces a frameshift leading to a premature stop, two codons downstream. The predicted translation product would consist of 54 amino acid residues. The parents were found to be heterozygous for the mutation. Conclusions Our results confirm that the combination of SSCP and HA represents a powerful tool to study the molecular defects causing analbuminemia in humans.