title: Exclusion of mutations in the PRNP, JPH3, TBP, ATN1, CREBBP, POU3F2 and FTL genes as a cause of disease in Portuguese patients with a Huntington-like phenotype.
abstract: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterised by chorea, cognitive impairment, dementia and personality changes, caused by the expansion of a CAG repeat in the HD gene. Often, patients with a similar clinical presentation do not carry expansions of the CAG repeat in this gene [Huntington disease-like (HDL) patients]. We report the genetic analysis of 107 Portuguese patients with an HDL phenotype. The HDL genes PRNP and JPH3, encoding the prion protein and junctophilin-3, respectively, were screened for repeat expansions in these patients. Given the partial clinical overlap of SCA17, DRPLA and neuroferritinopathy with HD, their causative genes (TBP, ATN1, and FTL, respectively) were also analysed. Finally, repeat expansions in two candidate genes, CREBBP and POU3F2, which encode the nuclear transcriptional coactivator CREB-binding protein and the CNS-specific transcription factor N-Oct-3, respectively, were also studied. Expansions of the repetitive tracts of the PRNP, JPH3, TBP, ATN1, CREBBP and POU3F2 genes were excluded in all patients, as were sequence alterations in the FTL gene. Since none of the genes already included in the differential diagnosis of HD was responsible for the disease in our sample, the genetic heterogeneity of the HDL phenotype is still open for investigation.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
authors.forename: Maria do Carmo
authors.initials: MDC
authors.lastname: Costa
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Teixeira-Castro
authors.affiliation: Department of Medicine, CHUM, Université de Montreal, Hôpital Notre-Dame, Montreal, Canada.
authors.forename: Marco
authors.initials: M
authors.lastname: Constante
authors.affiliation: Hospital Geral de Sto. António, Porto, Portugal.
authors.forename: Marina
authors.initials: M
authors.lastname: Magalhães
authors.affiliation: UnIGENe, Institute for Molecular and Cell Biology, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Magalhães
authors.affiliation: UnIGENe, Institute for Molecular and Cell Biology, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Cerqueira
authors.affiliation: Hospital Egas Moniz, Lisboa, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Vale
authors.affiliation: Hospital Júlio de Matos, Lisboa, Portugal.
authors.forename: Vitorina
authors.initials: V
authors.lastname: Passão
authors.affiliation: Hospital Pedro Hispano, Matosinhos, Portugal.
authors.forename: Célia
authors.initials: C
authors.lastname: Barbosa
authors.affiliation: Hospital Pediátrico de Coimbra, Coimbra, Portugal.
authors.forename: Conceição
authors.initials: C
authors.lastname: Robalo
authors.affiliation: Hospital de São Sebastião, Santa Maria da Feira, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Coutinho
authors.affiliation: Hospital Geral de Sto. António, Porto, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Barros
authors.affiliation: Department of Medicine, CHUM, Université de Montreal, Hôpital Notre-Dame, Montreal, Canada.|UnIGENe, Institute for Molecular and Cell Biology, Porto, Portugal.
authors.forename: Manuela M
authors.initials: MM
authors.lastname: Santos
authors.affiliation: UnIGENe, Institute for Molecular and Cell Biology, Porto, Portugal.|Department of Population Studies, ICBAS, University of Porto, Porto, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sequeiros
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal. pmaciel@ecsaude.uminho.pt.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Maciel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001052:Apoferritins; D050882:CREB-Binding Protein / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005293:Ferritins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D006816:Huntington Disease / Q000209:etiology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D050809:POU Domain Factors / Q000235:genetics; D010641:Phenotype; D011174:Portugal; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D035181:TATA-Box Binding Protein / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: C507433:FTL protein, human; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors; D035181:TATA-Box Binding Protein; C095278:atrophin-1; C412507:junctophilin; C085076:transcription factor Brn-2; D005293:Ferritins; D001052:Apoferritins; D050882:CREB-Binding Protein; C494363:CREBBP protein, human