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Disruption of NUBPL due to balanced translocation [t(3;14) (q26.33;q14)] increases severity of a family-specific PGK1 mutation

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dc.contributor.authorDavid, Dezső
dc.contributor.authorHaltrich, Iren
dc.contributor.authorMarques, Barbara
dc.contributor.authorFernandes, Cristina
dc.contributor.authorMalveiro, Sara
dc.contributor.authorFekete, György
dc.date.accessioned2013-09-17T11:10:17Z
dc.date.available2013-09-17T11:10:17Z
dc.date.issued2013-06
dc.description.abstractAn intriguing group of familiar translocations are those which not always segregate with the “associated” disorder. Here we report the genetic alterations underlying a clinical phenotype characterized by haemolytic anemia and neuro-myopathy, seemingly associated with the familial translocation [t(3;14)(3q26.33;q14)]. Two affected probands and two unaffected relatives have been identified as carriers of this translocation. The 3q26.33 breakpoint was mapped about 40 kb from the TTC14 5’ end, at position 180.28 Mb and the 14q14 breakpoint within IVS 6 of NUBPL. The latter has been implicated in the aetiology of mitochondrial complex I deficiency (OMIM 252010). The most important additional possible candidate gene identified in this region is DNAJC19 causing an autosomal recessive disorder (OMIM 610198) that partially overlaps the reported phenotype. The recognition that a deceased relative most likely suffered from a similar disorder suggested the possibility of an X-linked disorder. Exclusion of additional genomic alterations within the breakpoint regions or elsewhere in the genome, familial X-chromosome segregation analysis and whole exome sequencing identified a novel missense mutation, c.358G>A, p.Glu120Lys, in exon 4 of phosphoglycerate kinase 1 (PGK1). Segregation analysis confirmed the association of this mutation with the disease phenotype. Re-evaluation of clinical data indicates that myopathy is considerably more severe in PGK1 deficient patients carriers of the translocation. The confirmation of this observation is currently underway. In conclusion, we have identified a novel PGK1 mutation whose clinical phenotype is exacerbated by co-inheritance of the disrupted NUBPL and/or by alterations affecting the genes in the breakpoint regions.
dc.description.sponsorshipFundação para a Ciência e a Tecnologia
dc.identifier.citationEuropean Journal of Human Genetics. 2003;21(Suppl 2):263por
dc.identifier.issn1018-4813
dc.identifier.urihttp://hdl.handle.net/10400.18/1715
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherNature Publishing Group / European Society of Human Geneticspor
dc.relationPTDC/SAU-GMG/118140/2010 and PEst-OE/SAU/UI0009/2011
dc.relation.publisherversionhttps://www.eshg.org/fileadmin/www.eshg.org/conferences/2013/ESHG2013AbstractsWebsite.pdfpor
dc.subjectDoenças Genéticaspor
dc.subjectTranslocação Equilibradapor
dc.subjectMetabolic and mitochondrial disorders
dc.subjectTranslocation t(3;14)
dc.subjectPGK1 deficiency
dc.subjectNUBPL
dc.titleDisruption of NUBPL due to balanced translocation [t(3;14) (q26.33;q14)] increases severity of a family-specific PGK1 mutationpor
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceParis, Françapor
oaire.citation.endPage263por
oaire.citation.startPage263por
oaire.citation.titleEuropean Human Genetics Conference (ESHG 2013), 8-11 june 2013por
oaire.citation.volume21(Suppl 2)por
rcaap.rightsrestrictedAccesspor
rcaap.typeconferenceObjectpor

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