Molecular Genetics of Analbuminaemia

Abstract Congenital analbuminaemia (CAA) is a very rare condition manifested by the near complete absence of albumin, the major blood protein, because of defects in the albumin ( ALB ) gene. It is generally regarded as relatively benign in adults, but analbuminaemic individuals may be at risk during the perinatal and childhood period. Twenty‐one different molecular lesions in the ALB are now known as cause of the trait. These include one mutation in the start codon, one frameshift/insertion, five frameshift/deletions, seven nonsense mutations and seven mutations affecting splicing. Thus, nonsense mutations, mutations affecting splicing and frameshift/deletions seem to be the most common causes of CAA. These results indicate that the trait is an allelic heterogeneous disorder caused by homozygous or, in a single case, compound heterozygous inheritance of defects. Most mutations are unique, but one, named Kayseri, is responsible for about half of the known cases. Key Concepts: CAA is an autosomal recessive disorder. Apart from the possibility of premature atherosclerotic complications, the phenotype seems to be benign in adults. Analbuminaemic individuals may be at risk during the perinatal and the childhood period. CAA is caused by homozygous or, in a single case, compound heterozygous inheritance of abnormal albumin alleles from both parents. Twenty‐one different molecular defects in the ALB are known as cause of the trait. Nonsense mutations, mutations affecting splicing and frameshift/deletions are the most common causes of CAA. No evidence has so far been found for the presence in serum of the putative protein products produced as a consequence of the above 21 mutations. The molecular defects are located in nine different exons and in four different introns. This distribution seems to suggest that CAA is the result of widely scattered random sequence variations. The increasing knowledge of the causative defects seems to reveal the presence of regions in the ALB that are prone to mutations.