A nucleotide insertion and frameshift cause analbuminemia in an Italian family

Journal Article · Tue Mar 15 04:00:00 EST 1994 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.91.6.2275· OSTI ID:86520

Watkins, S; Madison, J; Putnam, F W ^[1]; Galliano, M ^[2]; Minchiotti, L ^[3]

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1. Indiania Univ., Bloomington, IN (United States)
2. Univ. of Sassari (Italy)
3. Univ. of Pavia (Italy)

In analbuminemia, a very rare inherited syndrome, subjects produce little or no albumin (1/100th to 1/1000th normal), presumably because of a mutation in the albumin gene; yet, they have only moderate edema and few related symptoms owing to a compensatory increase in other plasma proteins. Because of the virtual absence of albumin the defect must be identified at the DNA level. In this study the mutation causing analbuminemia in an Italian family was investigated by analysis of DNA from a mother and her daughter. The mother was homozygous for the trait and had a serum albumin value. Molecular cloning and sequence analysis of DNA from both mother and daughter showed that the mutation is caused by a nucleotide insertion in exon 8; this produces a frameshift leading to a premature stop, seven codons downstream. The methods of heteroduplex hybridization and single-strand conformation polymorphism were used to compare the DNA of the mother and daughter to the DNA of two unrelated analbumineimic inidivuduals (one italian and one American). This showed that all three analbuminemic individuals had different mutations; these also differed from the mutation in the only human case previously studied at the DNA level, which was a splicing defect affecting the ligation of the 6-exon y sequences. Thus, analbuminemia may result from a variety of mutations and is genetically heterogeneous. 33 refs., 5 figs., 1 tab.

• Sponsoring Organization: USDOE
• OSTI ID: 86520
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 6 Vol. 91; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ALBUMINS
DNA SEQUENCING
DNA-CLONING
GENE MUTATIONS
HEREDITARY DISEASES