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

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. 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. 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. Molecular diagnosis based on DHPLC and DNA sequencing represents a powerful tool to study molecular defects causing analbuminemia. [Display omitted] ► Updating of analbuminemia register and mutation spectrum. ► New strategy of analbuminemia mutation screening based on DHPLC and DNA sequencing. ► We discuss the hypothesis suggesting intron-exon junctions as mutational hot spot.