Detection of a novel splicing mutation causing analbuminemia in a Libyan family.

BACKGROUND AND OBJECTIVES: Analbuminemia is a very rare autosomal recessive disorder. It is an allelic heterogeneous defect caused by a variety of mutations within the albumin gene. We describe in this report two new cases of analbuminemia in Libyans. DESIGN AND METHODS: The 14 coding exons of the human serum albumin (HSA) gene and their intron-exon junctions were PCR amplified. The products were screened for mutations by Denaturing High Performance Liquid Chromatography (DHPLC). Samples with altered DHPLC profiles were sequenced. RESULTS: DNA sequencing revealed the presence of a novol homozygous G➔T transition in the first base of intron 11 (c.1428+1G>T), in both children. This mutation destroys the GT consensus donor sequence found at the 5' end of most intervening sequences and would cause the defective pre-mRNA splicing. CONCLUSION: Molecular diagnosis based on DHPLC and DNA sequencing represents a powerful tool to study molecular defects causing analbuminemia.