Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/2858
Título: Disruption of NUBPL due to balanced translocation [t(3;14)(q26.33;q14)] increases severity of a family-specific PGK1 mutation
Autor: David, Dezső
Haltrich, Iren
Marques, Barbara
Fernandes, Catarina
Malveiro, Sara
Fekete, György
Palavras-chave: Metabolic and Mitochondrial disorders
Translocation t(3;14)
PGK1 Deficiency
Doenças Genéticas
Data: Jun-2013
Editora: Nature Publishing Group (NPG)
Citação: European Jornal Of Human Genetics: Abstracts. 2013; 21(Suppl.2): 263
Resumo: An 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.
Peer review: yes
URI: http://hdl.handle.net/10400.18/2858
ISSN: 1018-4813
Versão do Editor: https://www.eshg.org/fileadmin/www.eshg.org/conferences/2013/ESHG2013AbstractsWebsite.pdf
Aparece nas colecções:DGH - Posters/abstracts em congressos internacionais

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