Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis

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 (7.8%), 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.

Hemiagenesis of the thyroid gland detected by coincidence—what is the clinical relevance?

“…FOXE1-polyAla tract expansion may thus contribute to familial, but not sporadic, forms of THA [30]. Cerqueira et al [31] performed a mutation screening in different genes (PAX-8, NKX2-5, TSH-R, HES-1) that are involved in thyroid development. In this study, no mutations were detected in any of the candidate genes [31].…”

“…Cerqueira et al [31] performed a mutation screening in different genes (PAX-8, NKX2-5, TSH-R, HES-1) that are involved in thyroid development. In this study, no mutations were detected in any of the candidate genes [31]. Castanet et al [32] screened a cohort of 22 patients with thyroid dysgenesis including THA and also found no PAX-8 mutations.…”

“…Thus, according to the current knowledge, THA is likely a polygenetic disorder. In addition, epigenetic factors may also be involved in the pathogenesis of THA [31,35].…”

“…Cerqueira et al. [ 31 ] performed a mutation screening in different genes (PAX‑8, NKX2‑5, TSH‑R, HES-1) that are involved in thyroid development. In this study, no mutations were detected in any of the candidate genes [ 31 ].…”

Features of the Distribution of Specific Markers of Thyrocyte Proliferation During Hepatic Cirrhosis

“…Определить способность к восстановлению тироцитов при утрате клеток фолликулярного и экстрафолликулярного эпителия возможно, оценив распределение основных маркеров пролиферации тироцитов. Известно, что к таковым относят тиреоидспецифический фактор транскрипции (thyroidtranscriptionfactor-1 (TTF-1)), который находится в тесном взаимодействии с другим фактором транскрипции, относящимся к семейству генов Pax8 (Pairedbox 8), участвующим в перестройке щитовидной железы, путем дифференциации тироцитов по определенному фенотипу [4,5]. Однако Pax8 может быть выявлен в эмбриональных тканях почек, нервной системы, что свидетельствует о его локализации в различных клетках, включая и зрелые тироциты [6]…”