APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family

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dc.contributor.authorDussaillant, Catalina
dc.contributor.authorSerrano Larrea, Valentina
dc.contributor.authorMaiz Gurruchaga, Manuel Alberto
dc.contributor.authorEyheramendy Duerr, Susana
dc.contributor.authorCataldo Bascuñan, Luis Rodrigo
dc.contributor.authorSmalley Meylan, Susan Valerie
dc.contributor.authorRigotti Rivera, Attilio
dc.contributor.authorRubio, Lorena.
dc.contributor.authorLagos Arévalo, Carlos Fernando
dc.contributor.authorSantos Martín, José Luis
dc.date.accessioned2019-10-17T14:43:17Z
dc.date.available2019-10-17T14:43:17Z
dc.date.issued2012
dc.date.updated2019-10-14T18:47:21Z
dc.description.abstractAbstract Background Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. Methods We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. Results A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. Conclusion The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.
dc.fuente.origenBiomed Central
dc.identifier.citationBMC Medical Genetics. 2012 Nov 15;13(1):106
dc.identifier.doi10.1186/1471-2350-13-106
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/26724
dc.issue.numeroNo. 106
dc.language.isoen
dc.pagina.final10
dc.pagina.inicio1
dc.revistaBMC Medical Geneticses_ES
dc.rightsacceso abierto
dc.rights.holderDussaillant et al.; licensee BioMed Central Ltd.
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.otherHipertrigliceridemia -Chile -estudio de casoses_ES
dc.subject.otherTriglicéridos - Análisises_ES
dc.subject.otherGenéticaes_ES
dc.titleAPOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous familyes_ES
dc.typeartículo
dc.volumenVol. 13
sipa.codpersvinculados11709
sipa.codpersvinculados99116
sipa.codpersvinculados82611
sipa.codpersvinculados1015508
sipa.codpersvinculados143948
sipa.codpersvinculados68489
sipa.codpersvinculados7337
sipa.codpersvinculados1005923
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