RESUMO
OBJECTIVE: To evaluate the candidate genes PAX-8, NKX2-5, TSH-R and HES-1 in 63 confirmed cases of thyroid dysgenesis. SUBJECTS AND METHODS: Characterization of patients with congenital hypothyroidism into specific subtypes of thyroid dysgenesis with hormone levels (TT4 and TSH), thyroid ultrasound and scintigraphy. DNA was extracted from peripheral blood leukocytes and the genetic analysis was realized by investigating the presence of mutations in the transcription factor genes involved in thyroid development. RESULTS: No mutations were detected in any of the candidate genes. In situ thyroid gland represented 71.1% of all cases of permanent primary congenital hypothyroidism, followed by hypoplasia (9.6%), ectopia (78%), hemiagenesis (6.0%) and agenesis (5.5%). The highest neonatal screening TSH levels were in the agenesis group (p < 0.001). CONCLUSIONS: Thyroid dysgenesis is possibly a polygenic disorder and epigenetic factors could to be implicated in these pathogeneses.
Assuntos
Proteína Homeobox Nkx-2.5/genética , Mutação/genética , Fator de Transcrição PAX8/genética , Receptores da Tireotropina/genética , Disgenesia da Tireoide/genética , Brasil , Pré-Escolar , Estudos de Coortes , Hipotireoidismo Congênito/diagnóstico por imagem , Hipotireoidismo Congênito/etiologia , Hipotireoidismo Congênito/genética , Análise Mutacional de DNA , Feminino , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Masculino , Triagem Neonatal , Disgenesia da Tireoide/complicações , Disgenesia da Tireoide/diagnóstico por imagem , Tireotropina/sangue , Tiroxina/sangue , Fatores de Transcrição HES-1/genética , UltrassonografiaRESUMO
ABSTRACT Objective: To evaluate the candidate genes PAX-8, NKX2-5, TSH-R and HES-1 in 63 confirmed cases of thyroid dysgenesis. Subjects and methods: Characterization of patients with congenital hypothyroidism into specific subtypes of thyroid dysgenesis with hormone levels (TT4 and TSH), thyroid ultrasound and scintigraphy. DNA was extracted from peripheral blood leukocytes and the genetic analysis was realized by investigating the presence of mutations in the transcription factor genes involved in thyroid development. Results: No mutations were detected in any of the candidate genes. In situ thyroid gland represented 71.1% of all cases of permanent primary congenital hypothyroidism, followed by hypoplasia (9.6%), ectopia (78%), hemiagenesis (6.0%) and agenesis (5.5%). The highest neonatal screening TSH levels were in the agenesis group (p < 0.001). Conclusions: Thyroid dysgenesis is possibly a polygenic disorder and epigenetic factors could to be implicated in these pathogeneses.