A novel splicing mutation causes analbuminemia in a Portuguese boy

Caridi, Gianluca; Dagnino, Monica; Duca, Marco Di; Pinto, Helena; Espinheira, Maria do Céu; Guerra, António; Fernandes, Susana; Campagnoli, Monica; Galliano, Monica; Minchiotti, Lorenzo

doi:10.1016/j.ymgme.2011.12.009

Cited by 13 publications

(20 citation statements)

References 28 publications

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“…Thus, these four splicing mutations did not cause a complete degradation of the variant mRNA. As in the present case, in analbuminemia Bartin and Guimarães the mutations resulted in the skipping of the preceding exon (19,21), whereas in analbuminemia Baghdad and Tripoli the consequence of the mutation on mRNA could not be evaluated (18,20). …”

Section: Discussionmentioning

confidence: 40%

“…The most common consequence of splicing mutations is skipping of one or more exons, followed by the activation of aberrant 5′ donor or acceptor splice sites and retention of full introns in mRNA (17). Among the eight splice-site mutations, five affect the GT consensus dinucleotide sequence at the donor intron splice site: Baghdad (c.79+1G>A) (18), Bartin (c.1428+2T>C) (19), Tripoli (c.1428+1G>T) (20), Guimarães (c.1289+1G>A) (21), and Ankara (present paper). Although the presence of truncated albumin molecules in the serum could never be evidenced in analbuminemic individuals, in all the four cases (Fondi, Bartin, Guimarães and Ankara) in which there was performed a search for mRNA, it could be isolated from white blood cells, which allowed for a verification of the splicing defects at the mRNA level (2 and present paper).…”

Section: Discussionmentioning

confidence: 81%

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Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene

et al. 2014

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Introduction:Congenital analbuminemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. It is an allelic heterogeneous defect, caused by variety of mutations within the albumin gene in homozygous or compound heterozygous state. Herein we report the clinical and molecular characterization of a new case of congenital analbuminemia diagnosed in a female newborn of consanguineous (first degree cousins) parents from Ankara, Turkey, who presented with a low albumin concentration (< 8 g/L) and severe clinical symptoms.Materials and methods:The albumin gene of the index case was screened by single-strand conformation polymorphism, heteroduplex analysis, and direct DNA sequencing. The effect of the splicing mutation was evaluated by examining the cDNA obtained by reverse transcriptase - polymerase chain reaction (RT-PCR) from the albumin mRNA extracted from proband’s leukocytes.Results:DNA sequencing revealed that the proband is homozygous, and both parents are heterozygous, for a novel G>A transition at position c.1652+1, the first base of intron 12, which inactivates the strongly conserved GT dinucleotide at the 5′ splice site consensus sequence of this intron. The splicing defect results in the complete skipping of the preceding exon (exon 12) and in a frame-shift within exon 13 with a premature stop codon after the translation of three mutant amino acid residues.Conclusions:Our results confirm the clinical diagnosis of congenital analbuminemia in the proband and the inheritance of the trait and contribute to shed light on the molecular genetics of analbuminemia.

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Section: Discussionmentioning

confidence: 40%

Section: Discussionmentioning

confidence: 81%

Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene

et al. 2014

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“…The Afula mutation represents the first case of a defect resulting in analbuminemia located in exon 1. Twenty‐one different mutations have been so far reported to cause analbuminemia in humans [3,4,9,19,20 and present paper]. Among them, nineteen have been found to cause analbuminemia at the homozygous state.…”

Section: Discussionmentioning

confidence: 97%

“…Among them, nineteen have been found to cause analbuminemia at the homozygous state. These include seven nonsense mutations, six mutations affecting splicing, five frame‐shift/deletions and one frame‐shift/insertion [3,4,9,19,20 and present paper]. Compound heterozygosity for the remaining two molecular defects, a nonsense mutation and a splice site mutation with subsequent reading frame‐shift, was found to cause analbuminemia in an Italian man [7].…”

Section: Discussionmentioning

confidence: 99%

“…These mild symptoms may not be easily recognised, and for this reason, the majority of cases are detected randomly by routine serum protein electrophoresis showing that the marked reduction of the ALB band is compensated by the increase in other serum proteins, of which the lipoproteins may assume many of the transport functions of the major blood protein. Although analbuminemia is thought to be associated with very few medical complications, hypercholesterolaemia is a common finding in most analbuminemic subjects and has been recently reported also in other unaffected members of their families [4]. Although there are very few reports of patients with congenital analbuminemia who have had long‐term follow‐up as adults, hypercholesterolaemia may have been responsible for some cases of premature coronary heart disease [6], and treatment with statins appears to be recommended [7,8].…”

Section: Introductionmentioning

confidence: 99%

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A novel mutation in the albumin gene (c.1A>C) resulting in analbuminemia

Caridi

Dagnino

Lugani

et al. 2012

Eur J Clin Investigation

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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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A novel splicing mutation causes analbuminemia in a Portuguese boy

Cited by 13 publications

References 28 publications

Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene

Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene

A novel mutation in the albumin gene (c.1A>C) resulting in analbuminemia

Molecular Genetics of Analbuminaemia

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