The Experts below are selected from a list of 123 Experts worldwide ranked by ideXlab platform

Lorenzo Minchiotti - One of the best experts on this subject based on the ideXlab platform.

  • a novel splicing mutation in the albumin gene c 270 1g t causes Analbuminaemia in a german infant
    Annals of Clinical Biochemistry, 2016
    Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Wolfgang Thomas, Francesca Lugani, Lorenzo Minchiotti
    Abstract:

    Congenital Analbuminaemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. The clinical diagnosis may be challenging because of the absence of unambiguous symptoms and because hypoalbuminemia may have many causes different from a genetic lack of the protein. We describe the clinical and molecular characterization of a new case of congenital Analbuminaemia in an infant of apparently non-consanguineous parents from Treves, Germany. For molecular diagnosis, we used our strategy, based on the screening of the albumin gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing, which revealed that the proband is homozygous and both parents are heterozygous, for a novel G > T transversion at nucleotide c.270+ 1, the first base of intron 3. The mutation inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. In conclusion, we report the clinical findings and the molecular defect of this case, which contributes to a better understanding of the biological mechanism of congenital Analbuminaemia.

  • A novel splicing mutation in the albumin gene (c.270+1G>T) causes Analbuminaemia in a German infant.
    Annals of clinical biochemistry, 2015
    Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Wolfgang Thomas, Francesca Lugani, Lorenzo Minchiotti
    Abstract:

    Congenital Analbuminaemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. The clinical diagnosis may be challenging because of the absence of unambiguous symptoms and because hypoalbuminemia may have many causes different from a genetic lack of the protein. We describe the clinical and molecular characterization of a new case of congenital Analbuminaemia in an infant of apparently non-consanguineous parents from Treves, Germany. For molecular diagnosis, we used our strategy, based on the screening of the albumin gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing, which revealed that the proband is homozygous and both parents are heterozygous, for a novel G > T transversion at nucleotide c.270+ 1, the first base of intron 3. The mutation inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. In conclusion, we report the clinical findings and the molecular defect of this case, which contributes to a better understanding of the biological mechanism of congenital Analbuminaemia.

  • eLS - Molecular Genetics of Analbuminaemia
    eLS, 2014
    Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Ulrich Kragh-hansen, Theodore Peters
    Abstract:

    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. Keywords: congenital Analbuminaemia; clinical consequences; molecular diagnosis; albumin gene; mutations; DNA sequence

  • molecular genetics of Analbuminaemia
    eLS, 2014
    Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Ulrich Kraghhansen, Theodore Peters
    Abstract:

    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. Keywords: congenital Analbuminaemia; clinical consequences; molecular diagnosis; albumin gene; mutations; DNA sequence

  • Congenital Analbuminaemia: molecular defects and biochemical and clinical aspects.
    Biochimica et biophysica acta, 2013
    Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Galliano, Ulrich Kragh-hansen, Theodore Peters
    Abstract:

    Abstract Background DNA and mRNA sequencing of the coding regions of the human albumin gene (ALB) and of its intron/exon junctions has revealed twenty-one different molecular defects causing congenital Analbuminaemia (CAA). Scope of review To describe the mutations in molecular terms and to present the current knowledge about the most important biochemical and clinical effects of CAA. Major conclusions CAA is rare, but its frequency seems to be significantly higher in restricted and minimally admixed populations. The condition affects especially the lipid metabolism but apart from a possible increased risk for atherosclerotic complications, it is generally associated with mild clinical symptoms in adults. By contrast, several reports indicate that analbuminaemic individuals may be at risk during the perinatal and childhood periods, in which they seem to show increased morbidity and mortality. The twenty-one causative defects include seven nonsense mutations, seven changes affecting splicing, five frame-shift/deletions, one frame-shift/insertion and one mutation in the start codon. These results indicate that the trait is an allelic heterogeneous disorder caused by homozygous (nineteen cases) or compound heterozygous (single case) inheritance of defects. Most mutations are unique, but one, named Kayseri, is responsible for about half of the known cases. General significance Study of the defects in the ALB resulting in CAA allows the identification of “hot spot” regions and contributes to understanding the molecular mechanism underlying the trait. Such studies could also give molecular information about different aspects of ALB regulation and shed light on the regulatory mechanisms involved in the synthesis of the protein. This article is part of a Special Issue entitled Serum Albumin.

Gianluca Caridi - One of the best experts on this subject based on the ideXlab platform.

  • a novel splicing mutation in the albumin gene c 270 1g t causes Analbuminaemia in a german infant
    Annals of Clinical Biochemistry, 2016
    Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Wolfgang Thomas, Francesca Lugani, Lorenzo Minchiotti
    Abstract:

    Congenital Analbuminaemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. The clinical diagnosis may be challenging because of the absence of unambiguous symptoms and because hypoalbuminemia may have many causes different from a genetic lack of the protein. We describe the clinical and molecular characterization of a new case of congenital Analbuminaemia in an infant of apparently non-consanguineous parents from Treves, Germany. For molecular diagnosis, we used our strategy, based on the screening of the albumin gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing, which revealed that the proband is homozygous and both parents are heterozygous, for a novel G > T transversion at nucleotide c.270+ 1, the first base of intron 3. The mutation inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. In conclusion, we report the clinical findings and the molecular defect of this case, which contributes to a better understanding of the biological mechanism of congenital Analbuminaemia.

  • A novel splicing mutation in the albumin gene (c.270+1G>T) causes Analbuminaemia in a German infant.
    Annals of clinical biochemistry, 2015
    Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Wolfgang Thomas, Francesca Lugani, Lorenzo Minchiotti
    Abstract:

    Congenital Analbuminaemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. The clinical diagnosis may be challenging because of the absence of unambiguous symptoms and because hypoalbuminemia may have many causes different from a genetic lack of the protein. We describe the clinical and molecular characterization of a new case of congenital Analbuminaemia in an infant of apparently non-consanguineous parents from Treves, Germany. For molecular diagnosis, we used our strategy, based on the screening of the albumin gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing, which revealed that the proband is homozygous and both parents are heterozygous, for a novel G > T transversion at nucleotide c.270+ 1, the first base of intron 3. The mutation inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. In conclusion, we report the clinical findings and the molecular defect of this case, which contributes to a better understanding of the biological mechanism of congenital Analbuminaemia.

  • eLS - Molecular Genetics of Analbuminaemia
    eLS, 2014
    Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Ulrich Kragh-hansen, Theodore Peters
    Abstract:

    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. Keywords: congenital Analbuminaemia; clinical consequences; molecular diagnosis; albumin gene; mutations; DNA sequence

  • molecular genetics of Analbuminaemia
    eLS, 2014
    Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Ulrich Kraghhansen, Theodore Peters
    Abstract:

    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. Keywords: congenital Analbuminaemia; clinical consequences; molecular diagnosis; albumin gene; mutations; DNA sequence

  • Congenital Analbuminaemia: molecular defects and biochemical and clinical aspects.
    Biochimica et biophysica acta, 2013
    Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Galliano, Ulrich Kragh-hansen, Theodore Peters
    Abstract:

    Abstract Background DNA and mRNA sequencing of the coding regions of the human albumin gene (ALB) and of its intron/exon junctions has revealed twenty-one different molecular defects causing congenital Analbuminaemia (CAA). Scope of review To describe the mutations in molecular terms and to present the current knowledge about the most important biochemical and clinical effects of CAA. Major conclusions CAA is rare, but its frequency seems to be significantly higher in restricted and minimally admixed populations. The condition affects especially the lipid metabolism but apart from a possible increased risk for atherosclerotic complications, it is generally associated with mild clinical symptoms in adults. By contrast, several reports indicate that analbuminaemic individuals may be at risk during the perinatal and childhood periods, in which they seem to show increased morbidity and mortality. The twenty-one causative defects include seven nonsense mutations, seven changes affecting splicing, five frame-shift/deletions, one frame-shift/insertion and one mutation in the start codon. These results indicate that the trait is an allelic heterogeneous disorder caused by homozygous (nineteen cases) or compound heterozygous (single case) inheritance of defects. Most mutations are unique, but one, named Kayseri, is responsible for about half of the known cases. General significance Study of the defects in the ALB resulting in CAA allows the identification of “hot spot” regions and contributes to understanding the molecular mechanism underlying the trait. Such studies could also give molecular information about different aspects of ALB regulation and shed light on the regulatory mechanisms involved in the synthesis of the protein. This article is part of a Special Issue entitled Serum Albumin.

Monica Galliano - One of the best experts on this subject based on the ideXlab platform.

  • a novel splicing mutation in the albumin gene c 270 1g t causes Analbuminaemia in a german infant
    Annals of Clinical Biochemistry, 2016
    Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Wolfgang Thomas, Francesca Lugani, Lorenzo Minchiotti
    Abstract:

    Congenital Analbuminaemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. The clinical diagnosis may be challenging because of the absence of unambiguous symptoms and because hypoalbuminemia may have many causes different from a genetic lack of the protein. We describe the clinical and molecular characterization of a new case of congenital Analbuminaemia in an infant of apparently non-consanguineous parents from Treves, Germany. For molecular diagnosis, we used our strategy, based on the screening of the albumin gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing, which revealed that the proband is homozygous and both parents are heterozygous, for a novel G > T transversion at nucleotide c.270+ 1, the first base of intron 3. The mutation inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. In conclusion, we report the clinical findings and the molecular defect of this case, which contributes to a better understanding of the biological mechanism of congenital Analbuminaemia.

  • A novel splicing mutation in the albumin gene (c.270+1G>T) causes Analbuminaemia in a German infant.
    Annals of clinical biochemistry, 2015
    Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Wolfgang Thomas, Francesca Lugani, Lorenzo Minchiotti
    Abstract:

    Congenital Analbuminaemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. The clinical diagnosis may be challenging because of the absence of unambiguous symptoms and because hypoalbuminemia may have many causes different from a genetic lack of the protein. We describe the clinical and molecular characterization of a new case of congenital Analbuminaemia in an infant of apparently non-consanguineous parents from Treves, Germany. For molecular diagnosis, we used our strategy, based on the screening of the albumin gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing, which revealed that the proband is homozygous and both parents are heterozygous, for a novel G > T transversion at nucleotide c.270+ 1, the first base of intron 3. The mutation inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. In conclusion, we report the clinical findings and the molecular defect of this case, which contributes to a better understanding of the biological mechanism of congenital Analbuminaemia.

  • eLS - Molecular Genetics of Analbuminaemia
    eLS, 2014
    Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Ulrich Kragh-hansen, Theodore Peters
    Abstract:

    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. Keywords: congenital Analbuminaemia; clinical consequences; molecular diagnosis; albumin gene; mutations; DNA sequence

  • molecular genetics of Analbuminaemia
    eLS, 2014
    Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Ulrich Kraghhansen, Theodore Peters
    Abstract:

    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. Keywords: congenital Analbuminaemia; clinical consequences; molecular diagnosis; albumin gene; mutations; DNA sequence

  • Congenital Analbuminaemia: molecular defects and biochemical and clinical aspects.
    Biochimica et biophysica acta, 2013
    Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Galliano, Ulrich Kragh-hansen, Theodore Peters
    Abstract:

    Abstract Background DNA and mRNA sequencing of the coding regions of the human albumin gene (ALB) and of its intron/exon junctions has revealed twenty-one different molecular defects causing congenital Analbuminaemia (CAA). Scope of review To describe the mutations in molecular terms and to present the current knowledge about the most important biochemical and clinical effects of CAA. Major conclusions CAA is rare, but its frequency seems to be significantly higher in restricted and minimally admixed populations. The condition affects especially the lipid metabolism but apart from a possible increased risk for atherosclerotic complications, it is generally associated with mild clinical symptoms in adults. By contrast, several reports indicate that analbuminaemic individuals may be at risk during the perinatal and childhood periods, in which they seem to show increased morbidity and mortality. The twenty-one causative defects include seven nonsense mutations, seven changes affecting splicing, five frame-shift/deletions, one frame-shift/insertion and one mutation in the start codon. These results indicate that the trait is an allelic heterogeneous disorder caused by homozygous (nineteen cases) or compound heterozygous (single case) inheritance of defects. Most mutations are unique, but one, named Kayseri, is responsible for about half of the known cases. General significance Study of the defects in the ALB resulting in CAA allows the identification of “hot spot” regions and contributes to understanding the molecular mechanism underlying the trait. Such studies could also give molecular information about different aspects of ALB regulation and shed light on the regulatory mechanisms involved in the synthesis of the protein. This article is part of a Special Issue entitled Serum Albumin.

Adrian David Marais - One of the best experts on this subject based on the ideXlab platform.

  • The Use of Simvastatin in Analbuminaemia
    Cardiovascular Drugs and Therapy, 2001
    Co-Authors: Lesley Jean Burgess, Adrian David Marais
    Abstract:

    Congenital Analbuminaemia, a rare disorder associated with defective albumin synthesis, is characterised by hyperlipidaemia. Administration of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGRI) to analbuminaemic rats have demonstrated no significant effect on plasma lipids, however no published information regarding HMGRI treatment could be found in human subjects. The efficacy, safety and tolerability of Simvastatin was thus investigated in 2 South African patients with Analbuminaemia, a 21 year old Caucasian male (H-B) and a 61 year old black male (A-K). In the case of A-K, the lipid profile responded predictably but H-B responded less that expected from general experience with Simvastatin. Both subjects, however, experienced a three- to five-fold increase in creatine kinase. The use of HMGRI's should thus be used cautiously in these patients and it may be advisable to reserve treatment for secondary prevention.

Monica Campagnoli - One of the best experts on this subject based on the ideXlab platform.

  • a novel splicing mutation in the albumin gene c 270 1g t causes Analbuminaemia in a german infant
    Annals of Clinical Biochemistry, 2016
    Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Wolfgang Thomas, Francesca Lugani, Lorenzo Minchiotti
    Abstract:

    Congenital Analbuminaemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. The clinical diagnosis may be challenging because of the absence of unambiguous symptoms and because hypoalbuminemia may have many causes different from a genetic lack of the protein. We describe the clinical and molecular characterization of a new case of congenital Analbuminaemia in an infant of apparently non-consanguineous parents from Treves, Germany. For molecular diagnosis, we used our strategy, based on the screening of the albumin gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing, which revealed that the proband is homozygous and both parents are heterozygous, for a novel G > T transversion at nucleotide c.270+ 1, the first base of intron 3. The mutation inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. In conclusion, we report the clinical findings and the molecular defect of this case, which contributes to a better understanding of the biological mechanism of congenital Analbuminaemia.

  • A novel splicing mutation in the albumin gene (c.270+1G>T) causes Analbuminaemia in a German infant.
    Annals of clinical biochemistry, 2015
    Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Wolfgang Thomas, Francesca Lugani, Lorenzo Minchiotti
    Abstract:

    Congenital Analbuminaemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. The clinical diagnosis may be challenging because of the absence of unambiguous symptoms and because hypoalbuminemia may have many causes different from a genetic lack of the protein. We describe the clinical and molecular characterization of a new case of congenital Analbuminaemia in an infant of apparently non-consanguineous parents from Treves, Germany. For molecular diagnosis, we used our strategy, based on the screening of the albumin gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing, which revealed that the proband is homozygous and both parents are heterozygous, for a novel G > T transversion at nucleotide c.270+ 1, the first base of intron 3. The mutation inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. In conclusion, we report the clinical findings and the molecular defect of this case, which contributes to a better understanding of the biological mechanism of congenital Analbuminaemia.

  • eLS - Molecular Genetics of Analbuminaemia
    eLS, 2014
    Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Ulrich Kragh-hansen, Theodore Peters
    Abstract:

    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. Keywords: congenital Analbuminaemia; clinical consequences; molecular diagnosis; albumin gene; mutations; DNA sequence

  • molecular genetics of Analbuminaemia
    eLS, 2014
    Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Ulrich Kraghhansen, Theodore Peters
    Abstract:

    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. Keywords: congenital Analbuminaemia; clinical consequences; molecular diagnosis; albumin gene; mutations; DNA sequence

  • A novel frame-shift deletion causing Analbuminaemia in an Italian paediatric patient.
    European journal of clinical investigation, 2010
    Co-Authors: Monica Dagnino, Gianluca Caridi, Monica Campagnoli, Monica Galliano, M. Marsciani, Ilaria Bettocchi, D Tassinari, Filippo Bernardi, F. Chiodo, Lorenzo Minchiotti
    Abstract:

    Eur J Clin Invest 2010; 40 (3): 281–284 Abstract Background  Analbuminaemia (OMIM #103600) is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. The trait is caused by a variety of mutations within the albumin gene. Design  We report here the clinical and molecular characterization of a new case of congenital Analbuminaemia in a 4-year-old Italian girl diagnosed on the basis of the low level of circulating albumin (= 10·0 g L−1). The albumin gene was screened by single-strand conformation polymorphism and heteroduplex analysis and the mutated region submitted to DNA sequencing. Results  The proband was found to be homozygous, and both parents heterozygous, for a novel deletion in exon 8 (c.920delT). The subsequent frame-shift should have given rise to a putative polypeptide chain of 304 amino acid residues, which we could not identify in the proband’s serum. Conclusions  A novel Analbuminaemia causing mutation was identified and characterized at the clinical level in a child. The molecular diagnosis of the trait is based on the rapid localization of the mutation within the albumin gene by single-strand conformation polymorphism and heteroduplex analysis, followed by DNA sequencing of the mutated region.