Splicing mutation in human hereditary analbuminemia.

Ruffner, Duane E.; Dugaiczyk, Achilles

doi:10.1073/pnas.85.7.2125

Cited by 46 publications

(41 citation statements)

References 29 publications

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“…The mutated gene would have produced a truncated albumin of only 273 residues, but no evidence for this product is available. This mutation differs from the exon splicing defect found in the only other case of human analbuminemia studied at the gene level (17) and from the 7-bp deletion observed in the albumin gene ofNagase analbuminemic rats (18). Further studies with DNA from several other human subjects indicated that each had a different, as yet unidentified, mutation.…”

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confidence: 83%

“…4). The (17). The putative translation product is presumably truncated by a stop codon at the exon 6/intron 6 junction resulting in a predicted protein product of about 24 kDa compared with 66.5 kDa for normal albumin.…”

Section: Resultsmentioning

confidence: 99%

“…In our study, using primers D41 and D42 (17) as allele-specific oligonucleotide probes under stringent hybridization conditions, we examined DNA from human placenta (wild-type), Roma, Daughter of Roma, Codogno (an unrelated Italian analbuminemia), and pAnalb 9.4 (a plasmid containing the splice junction from an analbuminemic American Indian girl) (17 8 (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

“…The paradox is that the albumin gene is subject to many neutral mutations (11)(12)(13)(14)(15)(16)); yet, analbuminemia, though tolerable, is extremely rare. It has been postulated (17) that the presence of albumin may be critical in fetal life and only a few analbuminemic individuals survive past the neonatal state; this could explain why analbuminemia is so rare in adults.…”

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confidence: 99%

“…Human serum albumin (HSA) consists of a single polypeptide chain of 585 amino acid residues cross-linked by 17 disulfide bonds into a series of loops (1). A principal function of albumin is to bind and transport many metals, metabolites, and ligands including pharmaceutical drugs.…”

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confidence: 99%

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A nucleotide insertion and frameshift cause analbuminemia in an Italian family.

Watkins

Madison

Galliano

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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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

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confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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A nucleotide insertion and frameshift cause analbuminemia in an Italian family.

Watkins

Madison

Galliano

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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Molecular Genetics of Analbuminaemia

Minchiotti

Caridi

Campagnoli

et al. 2014

Encyclopedia of Life Sciences

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Congenital analbuminaemia (CAA) is a very rare condition manifested by the near complete absence of albumin, the major blood protein, because of defects in the albumin ( ALB ) gene. It is generally regarded as relatively benign in adults, but analbuminaemic individuals may be at risk during the perinatal and childhood period. Twenty‐one different molecular lesions in the ALB are now known as cause of the trait. These include one mutation in the start codon, one frameshift/insertion, five frameshift/deletions, seven nonsense mutations and seven mutations affecting splicing. Thus, nonsense mutations, mutations affecting splicing and frameshift/deletions seem to be the most common causes of CAA. These results indicate that the trait is an allelic heterogeneous disorder caused by homozygous or, in a single case, compound heterozygous inheritance of defects. Most mutations are unique, but one, named Kayseri, is responsible for about half of the known cases. Key Concepts: CAA is an autosomal recessive disorder. Apart from the possibility of premature atherosclerotic complications, the phenotype seems to be benign in adults. Analbuminaemic individuals may be at risk during the perinatal and the childhood period. CAA is caused by homozygous or, in a single case, compound heterozygous inheritance of abnormal albumin alleles from both parents. Twenty‐one different molecular defects in the ALB are known as cause of the trait. Nonsense mutations, mutations affecting splicing and frameshift/deletions are the most common causes of CAA. No evidence has so far been found for the presence in serum of the putative protein products produced as a consequence of the above 21 mutations. The molecular defects are located in nine different exons and in four different introns. This distribution seems to suggest that CAA is the result of widely scattered random sequence variations. The increasing knowledge of the causative defects seems to reveal the presence of regions in the ALB that are prone to mutations.

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Mutations and polymorphisms of the gene of the major human blood protein, serum albumin

et al. 2008

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Communicated by Jürgen HorstWe have tabulated the 77 currently known mutations of the familiar human blood protein, serum albumin (ALB). A total of 65 mutations result in bisalbuminemia. Physiological and structural effects of these mutations are included where observed. Most of the changes are benign. The majority of them were detected upon clinical electrophoretic studies, as a result of a point mutation of a charged amino acid residue. Three were discovered by their strong binding of thyroxine or triiodothyronine. A total of 12 of the tabulated mutations result in analbuminemia, defined as a serum albumin concentration of o1 g/L. These were generally detected upon finding a low albumin concentration in patients with mild edema, and involve either splicing errors negating translation or premature stop codons producing truncated albumin molecules. A total of nine mutations, five of those with analbuminemia and four resulting in variants modified near the C-terminal end, cause frameshifts. Allotypes from three of the point mutations become N-glycosylated and one C-terminal frameshift mutation shows O-glycosylation. Hum Mutat 29(8), [1007][1008][1009][1010][1011][1012][1013][1014][1015][1016] 2008.

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Splicing mutation in human hereditary analbuminemia.

Cited by 46 publications

References 29 publications

A nucleotide insertion and frameshift cause analbuminemia in an Italian family.

A nucleotide insertion and frameshift cause analbuminemia in an Italian family.

Molecular Genetics of Analbuminaemia

Mutations and polymorphisms of the gene of the major human blood protein, serum albumin

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