Identification of a novel mutation in the ANGPTL3 gene in two families diagnosed of familial hypobetalipoproteinemia without APOB mutation
Por:
Martín-Campos J.M., Roig R., Mayoral C., Martinez S., Martí G., Arroyo J.A., Julve J., Blanco-Vaca F.
Publicada:
1 ene 2012
Resumen:
Background: Familial hypobetalipoproteinemia (FHBL), characterized by extremely low levels of plasma apolipoprotein (apo) B and cholesterol associated with low-density lipoproteins (LDLc), is considered to be an autosomal co-dominant disorder of heterogeneous origin. The main genetic disorder associated with FHBL consists of mutations in the APOB gene, while other less frequent forms are associated with mutations in NPC1L1, PCSK9, a still unidentified gene in 3p21.1-22 and, more recently, in ANGPTL3. Methods: We scanned for ANGPTL3 mutations in 4 unrelated Spanish families with FHBL criteria but negative for mutations in APOB. The entire coding region and intron-exon boundaries of the ANGPTL3 gene were amplified and sequenced. Results: Two probands were positive for the same frameshift mutation, a deletion of 5. bp in codon 121 in ANGPTL3, which produces a truncated protein of 122 residues. This mutation in homozygosis was associated in both families with combined hypolipidemia, characterized by low plasma apoB, low total, LDL and HDL cholesterol and low triglycerides. Conclusion: We confirm the existence of a new phenotype of FHBL, denominated familial combined hypolipidemia, which consist of a biochemical phenotype of low LDLc, low apoB, low TG and, unlike APOB mutations, low HDL cholesterol, due to a loss-of-function mutation in ANGPTL3. © 2011 Elsevier B.V.
Filiaciones:
Martín-Campos J.M.:
Institut d'Investigació Biomèdica (IIB) Sant Pau, Barcelona, Spain
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
Roig R.:
Institut d'Investigació Biomèdica (IIB) Sant Pau, Barcelona, Spain
Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
Mayoral C.:
Institut d'Investigació Biomèdica (IIB) Sant Pau, Barcelona, Spain
Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
Martinez S.:
Institut d'Investigació Biomèdica (IIB) Sant Pau, Barcelona, Spain
Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Martí G.:
Servei de Pediatria, Althaia Xarxa Assistencial, Manresa, Barcelona, Spain
Arroyo J.A.:
Servei de Medicina Interna, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Julve J.:
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
Blanco-Vaca F.:
Institut d'Investigació Biomèdica (IIB) Sant Pau, Barcelona, Spain
Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
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