Analbuminemia in a Swiss family is caused by a C --> T transition at nucleotide 4446 of the albumin gene.
OBJECTIVE
To define the molecular defect that causes analbuminemia in an apparently healthy boy, son of non-consanguineous Swiss parents.


METHODS
Total DNA, extracted from peripheral blood samples from the proband and from both parents, was PCR-amplified using oligonucleotide primers designed to amplify the 14 exons of the human albumin gene and the flanking intron regions. The products were screened for mutations by single-strand conformation polymorphism (SSCP) and heteroduplex analyses (HA) either directly or after digestion with restriction enzymes. The combination of these methods identified the abnormal fragment, which was then sequenced.


RESULTS
DNA sequence analysis identified in the homozygous proband a C --> T transition at nucleotide 4446. The mutation changes the codon CGA for Arg 114 to a stop codon TGA, resulting in premature termination and is therefore responsible for the analbuminemic trait. The same mutation has been previously reported to cause analbuminemia in an American female. The putative protein product would have a length of 113 residues. The parents were found to be heterozygous for the mutation.


CONCLUSIONS
Gel-based mutation detection and DNA sequencing confirmed the diagnosis of congenital analbuminemia in the proband. Our results show that the combination of SSCP and HA represents a powerful tool to study the molecular defects causing analbuminemia in humans.
Campagnoli
Monica
M
Department of Biochemistry A.Castellani, University of Pavia, viale Taramelli 3B, 27100 Pavia, Italy.
Sala
Alberto
A
Labò
Sara
S
Rossi
Antonio
A
Neuhaus
Thomas J
TJ
Braegger
Christian P
CP
Minchiotti
Lorenzo
L
Galliano
Monica
M
D000418:Albumins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D001796:Blood Protein Disorders / Q000208:ethnology / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D020180:Heteroduplex Analysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D013557:Switzerland; D044465:White People / Q000235:genetics*
D000418:Albumins