ECE2015 Guided Posters Thyroid – hypothyroidism (10 abstracts)
Nkx2.5 gene mutations are not associated with congenital heart defects in children with thyroid dysgenesis
Helton Estrela Ramos 1, , Taise Lima de Oliveira Cerqueira 2 , Yane Rocha Ramos 1 , Paula Leite 3 , Jailciele Santos 1 , Daniel San Martin 1 , Anabel Goes Costa 3 , Vladimir Fernandes 4 , Giorgia Strappa 1 , Mariana Souza de Jesus 1 , Tatiana Amorim 5 & Ana Marice Ladeia 3
1Universidade Federal da Bahia, Salvador, Bahia, Brazil; 2Centro de Pesquisa Gonçalo Moniz – FIOCRUZ, Salvador, Bahia, Brazil; 3Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil; 4Diagnoson – Grupo Fleury, Salvador, Bahia, Brazil; 5Associação de Pais e Amigos dos Excepcionais – APAE, Salvador, Bahia, Brazil.
Context: Several specific transcriptional factors, in view of their important role in thyroid organogenesis and thyroid specific gene expression, would be strong candidate genes for the etiology of TD. The homeobox transcription factor NKX2.5 was thought to be only required for the organogenesis of the heart tube. However, NKX2.5−/− embryos also exhibited a smaller outgrowing thyroid bud. Indeed, several loss of function mutations in NKX2.5 have been described in patients with congenital heart disease (CHD), and an Italian study has identified three mutations in patients with TD.
Objectives: To search for genetic alteration in NKX2.5 gene in patients presenting both TD/CHD and isolated TD.
Methods: Among 1051 neonates screened between 2001 and 2013, 851 children were identified with CH. Individual phenotypes were analyzed in 86 children with TD using thyroid function tests (TT4 and TSH), scintigraphy and ultrasound as diagnostic tools. Seven patients had CHD and TD. DNA was extracted from whole blood and NKX2.5 gene coding region was amplified by PCR and sequenced.
Results: CHD were found in 8.1% of patients with TD investigated. The mutation screening revealed two known polymorphisms in 48 patients with isolated TD or TD associated with CHD. None of them are predicted to result in codon change in conserved domain (p.Glu21; p.Gln181).
Conclusion: NKX2.5 mutations were not found in patients having TD or TD associated with CHD. NKX2.5 gene might not be a strong candidate gene for mutation screening in population based studies. It would be of interest to attempt to identify additional NKX2.5 downstream target genes and upstream signaling pathways for a more complete knowledge of the function of this homeobox protein during thyroid migration and morphogenesis.
Disclosure: Fundação de Amparo a Pesquisa do Estado da Bahia.
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Endocrine Abstracts
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