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 of <0.01 g/dl (about 1/500th normal); the daughter was heterozygous for the trait and had a nearly normal 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 analbuminemic individuals (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 exon 6-exon 7 sequences. Thus, analbuminemia may result from a variety of mutations and is genetically heterogeneous.Serum albumin is the most abundant secreted protein in the body; it comprises about 50%o of the total protein in serum where it has a normal concentration of 3.5-4.5 g/dl (1

Analbuminemia is a very rare recessive disorder in which subjects have little or no circulating albumin, although albumin is normally the most abundant plasma protein and has many functions. Analbuminemla is caused by a variety of mutations in the albumin gene and is exhibited only by subjects homozygous for the defect. Previously the mutation had been identified at the molecular level in only two human cases; in one case it resulted from an exon-splicing defect, and in the other case it was caused by a nucleotide insertion that caused a frameshift and premature stop codon. In this investigation we identified the mutations in three unrelated subjects from different countries. In each instance a single-nucleotide mutation produced a stop codon, but the mutations occurred at three different sites: (i) in an Italian male a C -> T transition at nt 2368 in the genomic sequence of albumin, (u) a C -. T transition at nt 4446 for an American female, and (iU) a G -+ A transition at nt 7708 in a Canadian male. The size of the albumin fragment that might have been produced for the three cases varied from 31-to 213-amino acid residues, but no evidence for a circulating albumin fragment was obtained. The paradox is that analbuminea is extremely rare (frequency <

This article offers statistical support for the contention that demographic risk factors influence the incidence of some women's experiencing violence more than others. Our results were generated using a binary probit model and 6,332 observations from the 1996 Australian Women's Safety Survey. For purposes of comparison, we identified a set of benchmark demographic characteristics as those occurring most frequently in the data set and estimated that if a woman were to have all of these characteristics, the probability she would have experienced violence in the past 12 months was 6.7%. We found that the risk varied with levels of postschool education, income, ethnic background, number and age of children, marital status, and age. Employment status, school-leaving age, and socioeconomic status had no statistically significant effect on the risk of experiencing violence once other factors were considered. This analysis may provide a basis for violence reduction and prevention programs.

Alloalbuminemia is rare and has a cumulative frequency of only 1 in 3000 in Europeans and Japanese. also occur in Japan. These results provide evidence for independent mutations at single sites in the albumin genome. The clustering of these and of several other amino acid exchanges in certain regions of the albumin molecule suggests two possibilities: that certain sites are hypermutable or that mutants involving certain sites are more subject to selection than mutants involving others.

Despite their rarity and physiologically neutral character, more inherited structural variants of serum albumin (alloalbumins) are known than for any other human protein except hemoglobin. Including three previously unreported examples described here, we have identified 13 different point substitutions in alloalbumins of Japanese origin. Of these only albumin B and two proalbumins have been reported in other ethnic groups, and these are the most common variants of European origin. Some alloalbumins of Asiatic origin, but not yet identified in Japanese, are present in diverse ethnic groups. An alloalbumin found in indigenes of New Guinea (lysine -* asparagine at position 313) is also present in Caucasians of various European descents. Albumin Lambadi, occurring in a tribal group in south India, has a mutation (glutamic acid -* lysine at position 501) also found as a rare variant in individuals of diverse ethnic origin resident on four continents. These results suggest that some alloalbumins with the same substitution may have originated by independent mutations in various populations. This, together with the apparent clustering of point substitutions in the protein structure, may reflect hypermutability of the albumin gene.Because of recent studies (1-17) more heritable structural variants of serum albumin (alloalbumins) are known than for any other human protein except hemoglobin. However, unlike the situation with hemoglobin variants, no adverse effect on molecular function has been attributed to alloalbumins. Alloalbuminemia is rare and has a cumulative frequency of only 1:3000 to 1:10,000 in most populations (18-25); thus, it is usually expressed in a heterozygous fashion. More than 100 alloalbumins that have been given geographical or tribal names have been identified by genetic screening (18)(19)(20), by blood donor surveys (21), or by clinical electrophoresis (22, 23), and at least 20 different sites of structural change have been determined (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Four types of alloalbumins have been identified: (i) a series of single-point mutants (1-7, 12-14, 16), (ii) several chain-termination mutants (10, 11), (iii) proalbumins (variants that retain a basic amino-terminal hexapeptide because of a mutation in the Arg-Arg propeptide sequence required for post-transcriptional processing) (8,15), and (iv) arginyl-albumin, a variant that begins with arginine followed by a polypeptide sequence of the usual length (585 amino acid residues) (ref. 17; C. B. Laurell and F.W.P., unpublished results).Recently we have undertaken a series of collaborative studies on alloalbumins from populations throughout the world (1-3, 5, 6). Our objectives have been to determine the structural changes and to correlate these with the molecular properties ofalbumin and with such genetic characteristics as the site and type of mutation, heritability, and frequency. In this paper we report structural studies on alloalbumins from eight unrelated Japanese residents of Japan or Hawaii and a...