Molecular Diagnosis of Analbuminemia: A New Case Caused by a Nonsense Mutation in the Albumin Gene

Dagnino, Monica; Caridi, Gianluca; Haenni, Ueli; Duss, Adrian; Aregger, Fabienne; Campagnoli, Monica; Galliano, Monica; Minchiotti, Lorenzo

doi:10.3390/ijms12117314

Cited by 10 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of course, physicians should rule out the presence of other more common causes which can lower the concentration of circulating ALB, such as gastrointestinal or renal losses, redistribution into extra-vascular compartments and hepatic dysfunction ( 3 , 5 - 7 ). In contrast to the first studies on this topic, which defined as “true” analbuminemic subjects only individuals with an ALB concentration < 1 g/L, we have more recently described several cases characterized by ALB concentrations around 10 g/L ( 7 - 11 ). Probably, an overestimation of the real ALB concentration at this low levels by serum protein electrophoresis or by dye-binding bromcresol green reagents ( 12 ) may explain this apparent discrepancy.…”

Section: Introductionmentioning

confidence: 72%

“…PCR amplification of the 14 segments containing exons and flanking regions of the ALB gene ( 2 ) was performed using specific set of primers as described by Watkins et al ( 18 ) and the conditions reported by Caridi et al ( 8 ). Single strand conformation polymorphism (SSCP) heteroduplex analysis (HA), and the preparation of PCR products for sequence analysis were performed essentially as previously described ( 8 , 11 , 20 ). Samples were subjected to automated DNA sequencing on an Applied Biosystems™ 3100 xl instrument (Thermo Fisher Scientific, Milano, Italy), and analyzed by Sequencer software (5.0 version, Gene Code Corporation, Ann Arbour MI, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The screening for mutations of the ALB from the DNA of the subjects of this study was carried out as previously reported ( 8 , 11 , 20 ), in order to confirm the clinical diagnosis of CAA. SSCP analysis allowed us to locate the causative mutation in the 309 bp fragment encompassing exon 5 and the adjacent intron–exon junctions amplified by using PCR primers A09A and A10A ( Figure 3 ).…”

Section: Case Descriptionmentioning

confidence: 99%

See 2 more Smart Citations

A nucleotide deletion and frame-shift cause analbuminemia in a Turkish family

et al. 2016

Self Cite

View full text Add to dashboard Cite

Congenital analbuminemia is an autosomal recessive disorder, in which albumin, the major blood protein, is present only in a minute amount. The condition is a rare allelic heterogeneous defect, only about seventy cases have been reported worldwide. To date, more than twenty different mutations within the albumin gene have been found to cause the trait. In our continuing study of the molecular genetics of congenital analbuminemia, we report here the clinical and biochemical findings and the mutation analysis of the gene in two Turkish infants. For the molecular analysis, we used our strategy, based on the screening of the gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing. The results showed that both patients are homozygous for the deletion of a cytosine residue in exon 5, in a stretch of four cytosines starting from nucleotide position 524 and ending at position 527 (NM_000477.5(ALB):c.527delC). The subsequent frame-shift inserts a stop codon in position 215, markedly reducing the size of the predicted protein product. The parents are both heterozygous for the same mutation, for which we propose the name Erzurum from the city of origin of the family. In conclusion, our results show that in this family congenital analbuminemia is caused by a novel frame-shift/deletion defect, confirm the inheritance of the trait, and contribute to advance our understanding of the molecular basis underlying this condition.

show abstract

Section: Introductionmentioning

confidence: 72%

Section: Methodsmentioning

confidence: 99%

Section: Case Descriptionmentioning

confidence: 99%

See 1 more Smart Citation

A nucleotide deletion and frame-shift cause analbuminemia in a Turkish family

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…This defect was identified in two unrelated analbuminemic subjects: a 5-year-old Moroccan girl, the first child of a couple of consanguineous (first-degree cousins) parents (Campagnoli et al, 2005b), and in a 45-year-old man, born in Beirut, Lebanon, to consanguineous parents (first-degree cousins) of Syrian origin, living in Switzerland. The family comes from As Suwayda, a mainly Druze town located in Southwestern Syria, close to the border with Jordan (Dagnino et al, 2011).…”

Section: Molecular Geneticsmentioning

confidence: 99%

Diagnosis, Phenotype, and Molecular Genetics of Congenital Analbuminemia

et al. 2019

Self Cite

View full text Add to dashboard Cite

Congenital analbuminemia (CAA) is an inherited, autosomal recessive disorder with an incidence of 1:1,000,000 live birth. Affected individuals have a strongly decreased concentration, or complete absence, of serum albumin. The trait is usually detected by serum protein electrophoresis and immunochemistry techniques. However, due to the existence of other conditions in which the albumin concentrations are very low or null, analysis of the albumin ( ALB ) gene is necessary for the molecular diagnosis. CAA can lead to serious consequences in the prenatal period, because it can cause miscarriages and preterm birth, which often is due to oligohydramnios and placental abnormalities. Neonatally and in early childhood the trait is a risk factor that can lead to death, mainly from fluid retention and infections in the lower respiratory tract. By contrast, CAA is better tolerated in adulthood. Clinically, in addition to the low level of albumin, the patients almost always have hyperlipidemia, but they usually also have mild oedema, reduced blood pressure and fatigue. The fairly mild symptoms in adulthood are due to compensatory increment of other plasma proteins. The condition is rare; clinically, only about 90 cases have been detected worldwide. Among these, 53 have been studied by sequence analysis of the ALB gene, allowing the identification of 27 different loss of function (LoF) pathogenic variants. These include a variant in the start codon, frame-shift/insertions, frame-shift/deletions, nonsense variants, and variants affecting splicing. Most are unique, peculiar for each affected family, but one, a frame-shift deletion called Kayseri, has been found to cause about one third of the known cases allowing to presume a founder effect. This review provides an overview of the literature about CAA, about supportive and additional physiological and pharmacological information obtained from albumin-deficient mouse and rat models and a complete and up-to-date dataset of the pathogenic variants identified in the ALB gene.

show abstract

“…The majority of the analbuminemia causing mutations is so far unique, having been found only in members of the same family. Exceptions to this rule are the analbuminemic traits Bethesda (c.412C>T) [3] and El Jadida (c.802G>T) [3,23], that have been both found in two unrelated individuals, and a c.228_229delAT (analbuminemia Kayseri) [3], that has been identified in fifteen subjects of eleven families belonging to geographically distant and apparently unrelated ethnic groups, thus accounting for about 40% of the cases characterised at the molecular level [24].…”

Section: Discussionmentioning

confidence: 99%