A novel frameshift deletion in the albumin gene causes analbuminemia in a young Turkish woman.
BACKGROUND
Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin. The analbuminemic trait was diagnosed in a young Turkish woman on the basis of her clinical symptoms (bilateral lower limb edema) and biochemical findings (minimal albumin amount and variable increases in other protein fractions).


METHODS
Total DNA from the analbuminemic proband and her parents was PCR-amplified using oligonucleotide primers designed to amplify the 14 exons of the albumin gene (ALB) and the flanking intron regions. The products were screened for mutations by single-strand conformation polymorphism (SSCP) and heteroduplex analyses (HA).


RESULTS
HA allowed the identification of the mutation site in exon 12. Direct DNA sequencing of this abnormal fragment revealed that the analbuminemic trait was caused by a homozygous CA deletion at nucleotide positions c. 1614-1615 in the codons for Cys538 and Thr539. The subsequent frameshift should give rise to a putative truncated albumin variant in which the sequence Cys(538)-Thr-Leu-Ser has been changed to Cys(538)-Thr-Phe-Stop. The parents were heterozygous for the same mutation.


CONCLUSIONS
Gel-based mutation detection and DNA sequencing substantiate the clinical diagnosis of congenital analbuminemia in our patient and show that the condition is caused by a novel mutation within the ALB gene. These results contribute to shed light on the molecular basis of this rare condition.
Dagnino
Monica
M
Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini IRCCS, Largo G. Gaslini 5, 16148 Genova, Italy.
Caridi
Gianluca
G
Aydin
Zeki
Z
Ozturk
Savas
S
Karaali
Zeynep
Z
Kazancioglu
Rumeyza
R
Cefle
Kivanc
K
Gursu
Meltem
M
Campagnoli
Monica
M
Galliano
Monica
M
Minchiotti
Lorenzo
L
D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006720:Homozygote; D006801:Humans; D017384:Sequence Deletion; D012709:Serum Albumin / Q000172:deficiency* / Q000235:genetics*; D014421:Turkey; D055815:Young Adult
D018389:Codon, Nonsense; D012709:Serum Albumin