Percorrer por autor "Fekete, György"
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- Clinical and genetic findings in Hungarian pediatric patients carrying chromosome 16p copy number variants and a review of the literaturePublication . Lengyel, Anna; Pinti, Éva; Pikó, Henriett; Jávorszky, Eszter; David, Dezső; Tihanyi, Mariann; Gönczi, Éva; Kiss, Eszter; Tóth, Zsuzsa; Tory, Kálmán; Fekete, György; Haltrich, IrénThe short arm of chromosome 16 (16p) is enriched for segmental duplications, making it susceptible to recurrent, reciprocal rearrangements implicated in the etiology of several phenotypes, including intellectual disability, speech disorders, developmental coordination disorder, autism spectrum disorders, attention deficit hyperactivity disorders, obesity and congenital skeletal disorders. In our clinical study 73 patients were analyzed by chromosomal microarray, and results were confirmed by fluorescence in situ hybridization or polymerase chain reaction. All patients underwent detailed clinical evaluation, with special emphasis on behavioral symptoms. 16p rearrangements were identified in 10 individuals. We found six pathogenic deletions and duplications of the recurrent regions within 16p11.2: one patient had a deletion of the distal 16p11.2 region associated with obesity, while four individuals had duplications, and one patient a deletion of the proximal 16p11.2 region. The other four patients carried 16p variations as second-site genomic alterations, acting as possible modifying genetic factors. We present the phenotypic and genotypic results of our patients and discuss our findings in relation to the available literature.
- Disruption of NUBPL due to balanced translocation [t(3;14) (q26.33;q14)] increases severity of a family-specific PGK1 mutationPublication . David, Dezső; Haltrich, Iren; Marques, Barbara; Fernandes, Cristina; Malveiro, Sara; Fekete, GyörgyAn 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.
- Disruption of NUBPL due to balanced translocation [t(3;14)(q26.33;q14)] increases severity of a family-specific PGK1 mutationPublication . David, Dezső; Haltrich, Iren; Marques, Barbara; Fernandes, Catarina; Malveiro, Sara; Fekete, GyörgyAn 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.