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Combined mutation screening of NKX2-5, GATA4, and TBX5 in congenital heart disease: multiple heterozygosity and novel mutations.
Granados-Riveron, Javier T; Pope, Mark; Bu'lock, Frances A; Thornborough, Christopher; Eason, Jacqueline; Setchfield, Kerry; Ketley, Ami; Kirk, Edwin P; Fatkin, Diane; Feneley, Michael P; Harvey, Richard P; Brook, J David.
Afiliación
  • Granados-Riveron JT; Institute of Genetics, School of Biology, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
Congenit Heart Dis ; 7(2): 151-9, 2012.
Article en En | MEDLINE | ID: mdl-22011241
ABSTRACT
Background. Variants of several genes encoding transcription modulators, signal transduction, and structural proteins are known to cause Mendelian congenital heart disease (CHD). NKX2-5 and GATA4 were the first CHD-causing genes identified by linkage analysis in large affected families. Mutations of TBX5 cause Holt-Oram syndrome, which includes CHD as a clinical feature. All three genes have a well-established role in cardiac development. Design. In order to investigate the possible role of multiple mutations in CHD, a combined mutation screening was performed in NKX2-5, GATA4, and TBX5 in the same patient cohort. Samples from a cohort of 331 CHD patients were analyzed by polymerase chain reaction, double high-performance liquid chromatography and sequencing in order to identify changes in the NKX2-5, GATA4, and TBX5 genes. Results. Two cases of multiple heterozygosity of putative disease-causing mutations were identified. One patient was found with a novel L122P NKX2-5 mutation in combination with the private A1443D mutation of MYH6. A patient heterozygote for a D425N GATA4 mutation carries also a private mutation of the MYH6 gene (V700M). Conclusions. In addition to reporting two novel mutations of NKX2-5 in CHD, we describe families where multiple individual mutations seem to have an additive effect over the pathogenesis of CHD. Our findings highlight the usefulness of multiple gene mutational analysis of large CHD cohorts.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas de Homeodominio / Proteínas de Dominio T Box / Factor de Transcripción GATA4 / Cardiopatías Congénitas Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Límite: Humans Idioma: En Revista: Congenit Heart Dis Asunto de la revista: CARDIOLOGIA Año: 2012 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas de Homeodominio / Proteínas de Dominio T Box / Factor de Transcripción GATA4 / Cardiopatías Congénitas Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Límite: Humans Idioma: En Revista: Congenit Heart Dis Asunto de la revista: CARDIOLOGIA Año: 2012 Tipo del documento: Article País de afiliación: Reino Unido