Abstract
Congenital analbuminemia is an autosomal recessive disorder, in which albumin, the major blood protein, is present only in a minute amount. The condition is a rare allelic heterogeneous defect, only about seventy cases have been reported worldwide. To date, more than twenty different mutations within the albumin gene have been found to cause the trait. In our continuing study of the molecular genetics of congenital analbuminemia, we report here the clinical and biochemical findings and the mutation analysis of the gene in two Turkish infants. For the molecular analysis, we used our strategy, based on the screening of the gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing. The results showed that both patients are homozygous for the deletion of a cytosine residue in exon 5, in a stretch of four cytosines starting from nucleotide position 524 and ending at position 527 (NM_000477.5(ALB):c.527delC). The subsequent frame-shift inserts a stop codon in position 215, markedly reducing the size of the predicted protein product. The parents are both heterozygous for the same mutation, for which we propose the name Erzurum from the city of origin of the family. In conclusion, our results show that in this family congenital analbuminemia is caused by a novel frame-shift/deletion defect, confirm the inheritance of the trait, and contribute to advance our understanding of the molecular basis underlying this condition.
Highlights
Human albumin (ALB; UniProt ID: P02768) represents just less than two-thirds of total serum proteins [1] and is encoded by a single gene
Homozygous or compound heterozygous mutations in this gene have been associated with congenital analbuminemia (CAA, OMIM 103600), which results in a significant reduction of the protein in the blood
The results showed that both probands are homozygous for the deletion of a cytosine residue in a stretch of four cytosines starting from nucleotide position 524 and ending at position 527 (NM_000477.5(ALB):c.527delC). (Figure 4)
Summary
Human albumin (ALB; UniProt ID: P02768) represents just less than two-thirds of total serum proteins [1] and is encoded by a single gene The main clinical symptoms in adult analbuminemic individuals are oedema, hypotension, fatigue and, mainly in adult females, lower-body lipodystrophy [1,3,5,6] These symptoms seem relatively mild with respect to the many and important roles of ALB, but its low concentration can be partially compensated for by an increase in the synthesis of other serum proteins [1,3,5,6]. The prevalence of the causative mutations at the heterozygous state is probably somewhat higher than hitherto believed (less than 1:1.000.000), since the most common among them, Kayseri (c228_229delAT), has an allele frequency of about 6:100.000 [16] This condition is rare in consideration that CAA may be a risk factor during the perinatal and the childhood period [17,18,19]. In our continuing study of the molecular basis of CAA, we describe here the clinical and biochemical findings in two analbuminemic Turkish children together with the screening for mutations of the ALB in their family
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