Hereditary Fructose Intolerance: Functional Study of Two Novel ALDOB Natural Variants and Characterization of a Partial Gene Deletion (580 views)
Hum Mutat (ISSN: 1059-7794, 1098-1004, 1098-1004electronic), 2010 Dec; 31(12): 1294-1303.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 5.956, 5-year impact factor: 6.212
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-78649595331&partnerID=40&md5=cbaebf995a0ca80bcd4bb00d789f3748
Keywords: Aldob Kinetic Analysis, Aldob Molecular Modeling, Hfi Molecular Diagnosis, Hfi Molecular Epidemiology, Intragenic Deletion, Missense Mutations, Fructose Bisphosphate Aldolase, Allele, Article, Case Report, Catalysis, Child, Female, Gene Deletion, Gene Sequence, Genetic Variability, Hereditary Fructose Intolerance, Human, Nucleotide Sequence, Priority Journal, School Child, Site Directed Mutagenesis, Symptom, Base Sequence, Circular Dichroism, Fatal Outcome, Fructose-Bisphosphate Aldolase, Gene Frequency, Infant, Molecular Sequence Data, Pedigree, Protein Structure, Secondary, Recombinant Proteins,
Affiliations:
*** IBB - CNR ***
CEINGE-Biotecnologie Avanzate S.C.a r.l., Napoli, Italy
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II Napoli, Italy
IRCCS-Fondazione SDN, Via E. Gianturco 113, 80143 Napoli, Italy
Unità Operativa di Pediatria, Ospedale S. Giovanni di Dio, Agrigento, Italy
Dipartimento di Pediatria, Università degli Studi di Napoli Federico II Napoli, Italy
Clinica Pediatrica, Ospedale S. Gerardo, Monza, Italy
Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy
Dipartimento delle Scienze Biologiche-Sezione Biostrutture e CNISM, Università degli Studi di Napoli Federico II Napoli, Italy
Unit Operativa di Pediatria, Ospedale S. Giovanni di Dio, Agrigento, Italy
References:
Not available.
Hum Mutat (ISSN: 1059-7794, 1098-1004, 1098-1004electronic), 2010 Dec; 31(12): 1294-1303.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 5.956, 5-year impact factor: 6.212
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-78649595331&partnerID=40&md5=cbaebf995a0ca80bcd4bb00d789f3748
Keywords: Aldob Kinetic Analysis, Aldob Molecular Modeling, Hfi Molecular Diagnosis, Hfi Molecular Epidemiology, Intragenic Deletion, Missense Mutations, Fructose Bisphosphate Aldolase, Allele, Article, Case Report, Catalysis, Child, Female, Gene Deletion, Gene Sequence, Genetic Variability, Hereditary Fructose Intolerance, Human, Nucleotide Sequence, Priority Journal, School Child, Site Directed Mutagenesis, Symptom, Base Sequence, Circular Dichroism, Fatal Outcome, Fructose-Bisphosphate Aldolase, Gene Frequency, Infant, Molecular Sequence Data, Pedigree, Protein Structure, Secondary, Recombinant Proteins,
Affiliations:
*** IBB - CNR ***
CEINGE-Biotecnologie Avanzate S.C.a r.l., Napoli, Italy
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II Napoli, Italy
IRCCS-Fondazione SDN, Via E. Gianturco 113, 80143 Napoli, Italy
Unità Operativa di Pediatria, Ospedale S. Giovanni di Dio, Agrigento, Italy
Dipartimento di Pediatria, Università degli Studi di Napoli Federico II Napoli, Italy
Clinica Pediatrica, Ospedale S. Gerardo, Monza, Italy
Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy
Dipartimento delle Scienze Biologiche-Sezione Biostrutture e CNISM, Università degli Studi di Napoli Federico II Napoli, Italy
Unit Operativa di Pediatria, Ospedale S. Giovanni di Dio, Agrigento, Italy
References:
Not available.
Hereditary Fructose Intolerance: Functional Study of Two Novel ALDOB Natural Variants and Characterization of a Partial Gene Deletion
Hereditary fructose intolerance (HFI) is an autosomal recessive metabolic disease caused by impaired functioning of human liver aldolase (ALDOB). At least 54 subtle/point mutations and only two large intragenic deletions have been found in the ALDOB gene. Here we report two novel ALDOB variants (p.R46W and p.Y343H) and an intragenic deletion that we found in patients with suspected HFI. The residual catalytic activity of the recombinant p.R46W and p.Y343H variants toward F1P was particularly altered. We also characterized a large intragenic deletion that we found in six unrelated patients. This is the first report of six unrelated patients sharing the same ALDOB deletion, thus indicating a founder effect for this allele in our geographic area. Because this deletion involves ALDOB exon 5, it can mimic worldwide common pathogenic genotypes, that is, homozygous p.A150P and p.A175D. Finally, the identification of only one ALDOB mutation in symptomatic patients suggests that HFI symptoms can, albeit rarely, appear also in heterozygotes. Therefore, an excessive and continuous fructose dietary intake may have deleterious effects even in apparently asymptomatic HFI carriers. Hum Mutat 31:1294-1303, 2010. (c) 2010Wiley-Liss, Inc.
Hereditary fructose intolerance (HFI) is an autosomal recessive metabolic disease caused by impaired functioning of human liver aldolase (ALDOB). At least 54 subtle/point mutations and only two large intragenic deletions have been found in the ALDOB gene. Here we report two novel ALDOB variants (p.R46W and p.Y343H) and an intragenic deletion that we found in patients with suspected HFI. The residual catalytic activity of the recombinant p.R46W and p.Y343H variants toward F1P was particularly altered. We also characterized a large intragenic deletion that we found in six unrelated patients. This is the first report of six unrelated patients sharing the same ALDOB deletion, thus indicating a founder effect for this allele in our geographic area. Because this deletion involves ALDOB exon 5, it can mimic worldwide common pathogenic genotypes, that is, homozygous p.A150P and p.A175D. Finally, the identification of only one ALDOB mutation in symptomatic patients suggests that HFI symptoms can, albeit rarely, appear also in heterozygotes. Therefore, an excessive and continuous fructose dietary intake may have deleterious effects even in apparently asymptomatic HFI carriers. Hum Mutat 31:1294-1303, 2010. (c) 2010Wiley-Liss, Inc.
Hereditary Fructose Intolerance: Functional Study of Two Novel ALDOB Natural Variants and Characterization of a Partial Gene Deletion
No results. |
580 views. Last view on Thursday 17 April 2025, 18:26:36
ibb.cnr.it
