Analbuminemia produced by a novel splicing mutation

Analbuminemia is a rare autosomal recessive disorder
manifested by the absence or severe reduction of circulating
human serum albumin in homozygous or compound
heterozygous individuals. It is an allelic heterogeneous
defect, caused by a variety of mutations within
the albumin gene. The analbuminemic condition was
diagnosed in a Turkish female infant on the basis of low
albumin concentration (9.0 g/L). The albumin gene
was screened by single-strand conformation polymorphism
and heteroduplex analysis and submitted to
direct sequencing. The proband was found to be homozygous
for a T>C transition at nucleotide 13381, the
2nd base of intron 11. The effect of this previously
unreported mutation, which inactivates the strongly
conserved GT dinucleotide at the 5 splice site consensus
sequence of intron 11, was evaluated by examining
the cDNA obtained by reverse transcription-PCR from
the albumin mRNA extracted from the proband leukocytes.
This analysis revealed that the mutation, named
Bartin for the geographical origin of the patient’s family,
results in the skipping of exon 11. The subsequent
frameshift within exon 12 originates a premature stop
codon located 5 codons downstream at position 411. The
predicted translation product would consist of 410
amino acids. This novel extensive cDNA alteration is
responsible for the analbuminemic trait.