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Monica Galliano - One of the best experts on this subject based on the ideXlab platform.
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a novel insertion c 1098dupt in the albumin gene causes Analbuminemia in a consanguineous family
European Journal of Medical Genetics, 2019Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Brigitte Rigat, Patrick Van Den Abeele, Valerie Layet, Mariesophie Gavard, Lorenzo MinchiottiAbstract:Congenital Analbuminemia (OMIM # 616000) is an extremely rare autosomal recessive disorder, caused by variations in the albumin gene (ALB), which is generally thought to be a relatively benign condition in adulthood, but seems to be potentially life threatening in the pre- and peri-natal period. The subject of our study was a consanguineous family, in which we identified two analbuminemic individuals. Mutation analysis of ALB revealed that both are homozygous for a previously unreported insertion in exon 9 (c.1098dupT), causing a subsequent frame-shift with the generation of a premature stop codon, and an aberrant truncated putative protein product, p.Val367fsTer12. This variation is present in heterozygous condition in several other members of the family. The phenotype and the molecular genetics of CAA are discussed.
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diagnosis phenotype and molecular genetics of congenital Analbuminemia
Frontiers in Genetics, 2019Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Ulrich KraghhansenAbstract: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, a condition which can be readily detected by serum protein electrophoresis. However, due to differential diagnoses, examination of the albumin gene is necessary for establishing the molecular diagnosis of the condition. CAA can lead to serious consequences in the pre- and peri-natal period, it can cause preterm birth and neonatal or early childhood death. 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. It is uncertain, whether the hyperlipidemia increases the risk for developing atherosclerosis or other diseases. Because of the lack of albumin, albumin-binding drugs should be administered with care. The condition is rare, and only about 90 cases have been detected worldwide. However, molecular analysis of the ALB gene by DNA and mRNA sequencing identified so far 27 different variations; most of them are loss of function (LoF) affecting splicing, nonsense and frameshift/deletions and insertions, but also a variation in the start codon was detected. 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.
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Diagnosis, Phenotype, and Molecular Genetics of Congenital Analbuminemia
Frontiers Media S.A., 2019Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Ulrich Kragh-hansenAbstract: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
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a novel splicing mutation in the albumin gene c 270 1g t causes analbuminaemia in a german infant
Annals of Clinical Biochemistry, 2016Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Wolfgang Thomas, Francesca Lugani, Lorenzo MinchiottiAbstract: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.
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a nucleotide deletion and frame shift cause Analbuminemia in a turkish family
Biochemia Medica, 2016Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Elif Yilmaz Gulec, Hasan Onal, Duzgun Kilic, Lorenzo MinchiottiAbstract: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.
Lorenzo Minchiotti - One of the best experts on this subject based on the ideXlab platform.
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recurrent hypoglycemia in a case of congenital Analbuminemia
Case reports in endocrinology, 2020Co-Authors: Martin Litzel, Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Francesca Lugani, Stefan FischliAbstract:In congenital Analbuminemia (CAA), mutations in the albumin gene result in a severe deficiency or absence of plasma albumin. Only about 90 cases have been reported to date, but the specific features of glucose and lipid metabolism in congenital Analbuminemia have only been studied in a rat model of Analbuminemia. We report the case of a female patient hospitalized for a streptococcal skin infection who showed recurrent hypoglycemia. A diagnosis of CAA was confirmed by mutation analysis and by the detection of a single base variation in the ALB gene. Hypoglycemia was first documented after a fasting period during acute illness. Recurrent hypoglycemia persisted despite good general condition and normal nutrition during antimicrobial therapy with moxifloxacin. Several contributing factors causing this hypoglycemia can be discussed. Individuals with CAA are prone to adverse drug effects caused by changes in drug-protein binding properties. It is unclear if specific changes of glucose and lipid metabolism in CAA constitute a risk factor for hypoglycemia.
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congenital Analbuminemia in a patient affected by hypercholesterolemia a case report
World Journal of Clinical Cases, 2019Co-Authors: Patrizia Suppressa, Lorenzo Minchiotti, Monica Campagnoli, Francesca Lugani, Concetta Carbonara, Teresa Troiano, Carlo SabbaAbstract:Background Congenital Analbuminemia (CAA) is a very rare disorder. Our data describes the clinical features and laboratory results of a new case established by mutation analysis of the albumin gene in a 39-year-old woman presenting with hypercholesterolemia. Our findings contribute to shed light on the molecular genetics of the disorder and confirm that safe and well tolerated hypocholesterolemic treatment with atorvastatin may be administered in dislipidemic patient with CAA in order to reduce their cardiovascular risk. Case summary Our patient presented with a history of hypercholesterolemia and referred asthenia and heaviness in both legs. She was born from healthy and non-consanguineous parents and her development was normal. She had not familiarity for early cardiovascular disease, and did not report personal history of hypertension, chronic kidney or liver diseases. Clinical laboratories results showed critically reduced value of albumin whereas other serum proteins were elevated. Main causes of hypoalbuminemia (proteinuria, inflammatory state and insufficient hepatic synthesis) were ruled out by normal procedures and laboratory tests. So the hypothesis of a CAA was tested through mutation analysis of the albumin gene that revealed a homozygous CA deletion in exon 12, at nucleotide positions c1614-1615. This finding brought to the diagnosis of CAA. Currently the patient receives Atorvastatin 20 mg od and undergoes clinical and laboratory follow-up every six months. She never needed albumin infusions. Conclusion Our experience shows how treatment with atorvastatin may be safely administered and well tolerated in patients affected by CAA.
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a novel insertion c 1098dupt in the albumin gene causes Analbuminemia in a consanguineous family
European Journal of Medical Genetics, 2019Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Brigitte Rigat, Patrick Van Den Abeele, Valerie Layet, Mariesophie Gavard, Lorenzo MinchiottiAbstract:Congenital Analbuminemia (OMIM # 616000) is an extremely rare autosomal recessive disorder, caused by variations in the albumin gene (ALB), which is generally thought to be a relatively benign condition in adulthood, but seems to be potentially life threatening in the pre- and peri-natal period. The subject of our study was a consanguineous family, in which we identified two analbuminemic individuals. Mutation analysis of ALB revealed that both are homozygous for a previously unreported insertion in exon 9 (c.1098dupT), causing a subsequent frame-shift with the generation of a premature stop codon, and an aberrant truncated putative protein product, p.Val367fsTer12. This variation is present in heterozygous condition in several other members of the family. The phenotype and the molecular genetics of CAA are discussed.
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diagnosis phenotype and molecular genetics of congenital Analbuminemia
Frontiers in Genetics, 2019Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Ulrich KraghhansenAbstract: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, a condition which can be readily detected by serum protein electrophoresis. However, due to differential diagnoses, examination of the albumin gene is necessary for establishing the molecular diagnosis of the condition. CAA can lead to serious consequences in the pre- and peri-natal period, it can cause preterm birth and neonatal or early childhood death. 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. It is uncertain, whether the hyperlipidemia increases the risk for developing atherosclerosis or other diseases. Because of the lack of albumin, albumin-binding drugs should be administered with care. The condition is rare, and only about 90 cases have been detected worldwide. However, molecular analysis of the ALB gene by DNA and mRNA sequencing identified so far 27 different variations; most of them are loss of function (LoF) affecting splicing, nonsense and frameshift/deletions and insertions, but also a variation in the start codon was detected. 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.
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Diagnosis, Phenotype, and Molecular Genetics of Congenital Analbuminemia
Frontiers Media S.A., 2019Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Ulrich Kragh-hansenAbstract: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
Monica Campagnoli - One of the best experts on this subject based on the ideXlab platform.
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recurrent hypoglycemia in a case of congenital Analbuminemia
Case reports in endocrinology, 2020Co-Authors: Martin Litzel, Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Francesca Lugani, Stefan FischliAbstract:In congenital Analbuminemia (CAA), mutations in the albumin gene result in a severe deficiency or absence of plasma albumin. Only about 90 cases have been reported to date, but the specific features of glucose and lipid metabolism in congenital Analbuminemia have only been studied in a rat model of Analbuminemia. We report the case of a female patient hospitalized for a streptococcal skin infection who showed recurrent hypoglycemia. A diagnosis of CAA was confirmed by mutation analysis and by the detection of a single base variation in the ALB gene. Hypoglycemia was first documented after a fasting period during acute illness. Recurrent hypoglycemia persisted despite good general condition and normal nutrition during antimicrobial therapy with moxifloxacin. Several contributing factors causing this hypoglycemia can be discussed. Individuals with CAA are prone to adverse drug effects caused by changes in drug-protein binding properties. It is unclear if specific changes of glucose and lipid metabolism in CAA constitute a risk factor for hypoglycemia.
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congenital Analbuminemia in a patient affected by hypercholesterolemia a case report
World Journal of Clinical Cases, 2019Co-Authors: Patrizia Suppressa, Lorenzo Minchiotti, Monica Campagnoli, Francesca Lugani, Concetta Carbonara, Teresa Troiano, Carlo SabbaAbstract:Background Congenital Analbuminemia (CAA) is a very rare disorder. Our data describes the clinical features and laboratory results of a new case established by mutation analysis of the albumin gene in a 39-year-old woman presenting with hypercholesterolemia. Our findings contribute to shed light on the molecular genetics of the disorder and confirm that safe and well tolerated hypocholesterolemic treatment with atorvastatin may be administered in dislipidemic patient with CAA in order to reduce their cardiovascular risk. Case summary Our patient presented with a history of hypercholesterolemia and referred asthenia and heaviness in both legs. She was born from healthy and non-consanguineous parents and her development was normal. She had not familiarity for early cardiovascular disease, and did not report personal history of hypertension, chronic kidney or liver diseases. Clinical laboratories results showed critically reduced value of albumin whereas other serum proteins were elevated. Main causes of hypoalbuminemia (proteinuria, inflammatory state and insufficient hepatic synthesis) were ruled out by normal procedures and laboratory tests. So the hypothesis of a CAA was tested through mutation analysis of the albumin gene that revealed a homozygous CA deletion in exon 12, at nucleotide positions c1614-1615. This finding brought to the diagnosis of CAA. Currently the patient receives Atorvastatin 20 mg od and undergoes clinical and laboratory follow-up every six months. She never needed albumin infusions. Conclusion Our experience shows how treatment with atorvastatin may be safely administered and well tolerated in patients affected by CAA.
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a novel insertion c 1098dupt in the albumin gene causes Analbuminemia in a consanguineous family
European Journal of Medical Genetics, 2019Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Brigitte Rigat, Patrick Van Den Abeele, Valerie Layet, Mariesophie Gavard, Lorenzo MinchiottiAbstract:Congenital Analbuminemia (OMIM # 616000) is an extremely rare autosomal recessive disorder, caused by variations in the albumin gene (ALB), which is generally thought to be a relatively benign condition in adulthood, but seems to be potentially life threatening in the pre- and peri-natal period. The subject of our study was a consanguineous family, in which we identified two analbuminemic individuals. Mutation analysis of ALB revealed that both are homozygous for a previously unreported insertion in exon 9 (c.1098dupT), causing a subsequent frame-shift with the generation of a premature stop codon, and an aberrant truncated putative protein product, p.Val367fsTer12. This variation is present in heterozygous condition in several other members of the family. The phenotype and the molecular genetics of CAA are discussed.
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diagnosis phenotype and molecular genetics of congenital Analbuminemia
Frontiers in Genetics, 2019Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Ulrich KraghhansenAbstract: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, a condition which can be readily detected by serum protein electrophoresis. However, due to differential diagnoses, examination of the albumin gene is necessary for establishing the molecular diagnosis of the condition. CAA can lead to serious consequences in the pre- and peri-natal period, it can cause preterm birth and neonatal or early childhood death. 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. It is uncertain, whether the hyperlipidemia increases the risk for developing atherosclerosis or other diseases. Because of the lack of albumin, albumin-binding drugs should be administered with care. The condition is rare, and only about 90 cases have been detected worldwide. However, molecular analysis of the ALB gene by DNA and mRNA sequencing identified so far 27 different variations; most of them are loss of function (LoF) affecting splicing, nonsense and frameshift/deletions and insertions, but also a variation in the start codon was detected. 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.
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Diagnosis, Phenotype, and Molecular Genetics of Congenital Analbuminemia
Frontiers Media S.A., 2019Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Ulrich Kragh-hansenAbstract: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
Gianluca Caridi - One of the best experts on this subject based on the ideXlab platform.
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recurrent hypoglycemia in a case of congenital Analbuminemia
Case reports in endocrinology, 2020Co-Authors: Martin Litzel, Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Francesca Lugani, Stefan FischliAbstract:In congenital Analbuminemia (CAA), mutations in the albumin gene result in a severe deficiency or absence of plasma albumin. Only about 90 cases have been reported to date, but the specific features of glucose and lipid metabolism in congenital Analbuminemia have only been studied in a rat model of Analbuminemia. We report the case of a female patient hospitalized for a streptococcal skin infection who showed recurrent hypoglycemia. A diagnosis of CAA was confirmed by mutation analysis and by the detection of a single base variation in the ALB gene. Hypoglycemia was first documented after a fasting period during acute illness. Recurrent hypoglycemia persisted despite good general condition and normal nutrition during antimicrobial therapy with moxifloxacin. Several contributing factors causing this hypoglycemia can be discussed. Individuals with CAA are prone to adverse drug effects caused by changes in drug-protein binding properties. It is unclear if specific changes of glucose and lipid metabolism in CAA constitute a risk factor for hypoglycemia.
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a novel insertion c 1098dupt in the albumin gene causes Analbuminemia in a consanguineous family
European Journal of Medical Genetics, 2019Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Brigitte Rigat, Patrick Van Den Abeele, Valerie Layet, Mariesophie Gavard, Lorenzo MinchiottiAbstract:Congenital Analbuminemia (OMIM # 616000) is an extremely rare autosomal recessive disorder, caused by variations in the albumin gene (ALB), which is generally thought to be a relatively benign condition in adulthood, but seems to be potentially life threatening in the pre- and peri-natal period. The subject of our study was a consanguineous family, in which we identified two analbuminemic individuals. Mutation analysis of ALB revealed that both are homozygous for a previously unreported insertion in exon 9 (c.1098dupT), causing a subsequent frame-shift with the generation of a premature stop codon, and an aberrant truncated putative protein product, p.Val367fsTer12. This variation is present in heterozygous condition in several other members of the family. The phenotype and the molecular genetics of CAA are discussed.
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Diagnosis, Phenotype, and Molecular Genetics of Congenital Analbuminemia
Frontiers Media S.A., 2019Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Ulrich Kragh-hansenAbstract: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
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diagnosis phenotype and molecular genetics of congenital Analbuminemia
Frontiers in Genetics, 2019Co-Authors: Lorenzo Minchiotti, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Ulrich KraghhansenAbstract: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, a condition which can be readily detected by serum protein electrophoresis. However, due to differential diagnoses, examination of the albumin gene is necessary for establishing the molecular diagnosis of the condition. CAA can lead to serious consequences in the pre- and peri-natal period, it can cause preterm birth and neonatal or early childhood death. 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. It is uncertain, whether the hyperlipidemia increases the risk for developing atherosclerosis or other diseases. Because of the lack of albumin, albumin-binding drugs should be administered with care. The condition is rare, and only about 90 cases have been detected worldwide. However, molecular analysis of the ALB gene by DNA and mRNA sequencing identified so far 27 different variations; most of them are loss of function (LoF) affecting splicing, nonsense and frameshift/deletions and insertions, but also a variation in the start codon was detected. 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.
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a novel splicing mutation in the albumin gene c 270 1g t causes analbuminaemia in a german infant
Annals of Clinical Biochemistry, 2016Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Wolfgang Thomas, Francesca Lugani, Lorenzo MinchiottiAbstract: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.
Monica Dagnino - One of the best experts on this subject based on the ideXlab platform.
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congenital Analbuminemia caused by a novel aberrant splicing in the albumin gene
Biochemia Medica, 2014Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Dagnino, Marco Di Duca, Omer Erdeve, Duran Yildiz, Serdar Alan, Begum Atasay, Saadet Arsan, Monica GallianoAbstract: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 ( 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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a novel mutation in the albumin gene c 1a c resulting in Analbuminemia
European Journal of Clinical Investigation, 2013Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Francesca Lugani, Monica Dagnino, Stavit A Shalev, Ronen Spiegel, Lorenzo MinchiottiAbstract:Eur J Clin Invest 2012 Abstract Background Analbuminemia (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 characterisation of two new cases of congenital Analbuminemia diagnosed in two members of the Druze population living in a Galilean village (Northern Israel) on the basis of their low level of circulating albumin. The albumin gene was screened by single-strand conformation polymorphism and heteroduplex analysis, and the mutated region was submitted to DNA sequencing. Results Both the analbuminemic subjects resulted homozygous for a previously unreported c.1 A>C transversion, for which we suggest the name Afula from the hospital where the two cases were investigated. This mutation causes the loss of the primary start codon ATG for Met1, which is replaced by a – then untranslated – triplet CTG for Leu. (p.Met1Leu). The use of an alternative downstream ATG codon would probably give rise to a completely aberrant polypeptide chain, leading to a misrouted intracellular transport and a premature degradation. Conclusions The discovery of this new ALB mutation, probably inherited from a common ancestor, sheds light on the molecular mechanism underlying the analbuminemic trait and may serve in the development of a rapid genetic test for the identification of a-symptomatic heterozygous carriers in the Druze population in the Galilee.
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a novel splicing mutation causes Analbuminemia in a portuguese boy
Molecular Genetics and Metabolism, 2012Co-Authors: Gianluca Caridi, Monica Campagnoli, Monica Galliano, Monica Dagnino, Marco Di Duca, Helena Pinto, Maria Do Ceu Espinheira, Antonio Guerra, Susana Fernandes, Lorenzo MinchiottiAbstract:Abstract Analbuminemia is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. It is an allelic heterogeneous defect, caused by a variety of mutations within the albumin gene. The analbuminemic condition was suspected in a Portuguese boy who presented with low albumin level (about 3.8 g/L) and a significant hypercholesterolemia, but with no clinical findings. The albumin gene was screened by single strand conformational polymorphism and heteroduplex analysis and submitted to direct DNA sequencing. The proband was found to be homozygous for a previously unreported G > A change at position c.1289 + 1, the first base of intron 10, which inactivates the strongly conserved GT dinucleotide at the 5′ splice site consensus sequence of the intron. The effect of this mutation was evaluated by examining the cDNA obtained by RT-PCR from the albumin mRNA extracted from proband's leukocytes. The splicing defect results in the skipping of the preceding exon. The subsequent reading frame-shift in exon 11 produces a premature stop codon located 33 codons downstream the 5′ end of the exon. This extensive cDNA alteration is responsible for the analbuminemic trait. Both parents were found to be heterozygous for the same mutation. DNA and cDNA sequence analysis established the diagnosis of congenital Analbuminemia in the proband. The effects of the so far identified splice-site mutations in the albumin gene are discussed.
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molecular diagnosis of Analbuminemia a new case caused by a nonsense mutation in the albumin gene
International Journal of Molecular Sciences, 2011Co-Authors: Monica Dagnino, Gianluca Caridi, Monica Campagnoli, Monica Galliano, Ueli Haenni, Adrian Duss, Fabienne Aregger, Lorenzo MinchiottiAbstract:Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin (ALB). We report here a new case diagnosed in a 45 years old man of Southwestern Asian origin, living in Switzerland, on the basis of his low ALB concentration (0.9 g/L) in the absence of renal or gastrointestinal protein loss, or liver dysfunction. The clinical diagnosis was confirmed by a mutational analysis of the albumin (ALB) gene, carried out by single-strand conformational polymorphism (SSCP), heteroduplex analysis (HA), and DNA sequencing. This screening of the ALB gene revealed that the proband is homozygous for two mutations: the insertion of a T in a stretch of eight Ts spanning positions c.1289 + 23–c.1289 + 30 of intron 10 and a c.802 G > T transversion in exon 7. Whereas the presence of an additional T in the poly-T tract has no direct deleterious effect, the latter nonsense mutation changes the codon GAA for Glu244 to the stop codon TAA, resulting in a premature termination of the polypeptide chain. The putative protein product would have a length of only 243 amino acid residues instead of the normal 585 found in the mature serum albumin, but no evidence for the presence in serum of such a truncated polypeptide chain could be obtained by two dimensional electrophoresis and western blotting analysis.
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a novel frameshift deletion in the albumin gene causes Analbuminemia in a young turkish woman
Clinica Chimica Acta, 2010Co-Authors: Monica Dagnino, Gianluca Caridi, Monica Campagnoli, Zeki Aydin, Savas Ozturk, Zeynep Karaali, Rumeyza Kazancioglu, Kivanc Cefle, Meltem Gursu, Monica GallianoAbstract:Abstract Background Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin. The analbuminemic trait was diagnosed in a young Turkish woman on the basis of her clinical symptoms (bilateral lower limb edema) and biochemical findings (minimal albumin amount and variable increases in other protein fractions). Methods Total DNA from the analbuminemic proband and her parents was PCR-amplified using oligonucleotide primers designed to amplify the 14 exons of the albumin gene (ALB) and the flanking intron regions. The products were screened for mutations by single-strand conformation polymorphism (SSCP) and heteroduplex analyses (HA). Results HA allowed the identification of the mutation site in exon 12. Direct DNA sequencing of this abnormal fragment revealed that the analbuminemic trait was caused by a homozygous CA deletion at nucleotide positions c. 1614–1615 in the codons for Cys538 and Thr539. The subsequent frameshift should give rise to a putative truncated albumin variant in which the sequence Cys(538)-Thr-Leu-Ser has been changed to Cys(538)-Thr-Phe-Stop. The parents were heterozygous for the same mutation. Conclusions Gel-based mutation detection and DNA sequencing substantiate the clinical diagnosis of congenital Analbuminemia in our patient and show that the condition is caused by a novel mutation within the ALB gene. These results contribute to shed light on the molecular basis of this rare condition.