Mutations in the gene encoding paired box domain (PAX8) are not a frequent cause of congenital hypothyroidism (CH) in Iranian patients with thyroid dysgenesis

Abstract

Objective: Congenital hypothyroidism (CH) may be caused by defects in the thyroid or in one of the stages in the synthesis of thyroid hormones. Thyroid dysgenesis may be associated with mutation in the paired box transcription factor 8 (PAX8) gene. We attempted to screen PAX8 gene mutation in 50 CH patients with thyroid dysgenesis. Subjects and methods: The patients were classified in two groups as agenesis and ectopic based on biochemical and para clinical tests. By employing PCR, Single Strand Conformation Polymorphism (SSCP) and sequencing, exons 3 to 12 of PAX8 gene with their exon-intron boundaries were studied. Results: No mutation was found in these patients in any of the exons. Conclusion: Our results, once again, indicate that the PAX8 mutation rate is very low and can only explain a minority of the cases. Therefore, it is highly needed to further investigate the genes controlling development and function of thyroid. Arq Bras Endocrinol Metab. 2010;54(6):555-9 Keywords Congenital hypothyroidism; thyroid dysgenesis; PAX8; gene mutation ReSumo Objetivo: O hipotireoidismo congênito (HC) pode ser causado por defeitos na formação da tireoide ou em uma das etapas da síntese dos hormônios tireoidianos. A disgenesia da tireoide pode ser associada a mutações no fator de transcrição PAX8. Neste estudo, foram rastreadas mutações no gene PAX8 em 50 pacientes com CH com disgenesia da tireoide. Sujeitos e méto-dos: Os pacientes foram classificados em dois grupos, com agenesia ou com ectopia, segundo os testes bioquímicos e paraclínicos. Foram empregadas as técnicas de SSCP (Single Strand Conformation Polymorphism) e sequenciamento para analisar os éxons 3 a 12 do gene PAX8 e suas bordas éxon-intron. Resultados: Nenhuma mutação foi encontrada nesses pacientes, em qualquer um dos éxons. Conclusão: Nossos resultados, mais uma vez, indicam que a taxa de mutação PAX8 é muito baixa e só pode explicar a minoria dos casos. Portanto, é altamente necessário investigar outros genes que controlam o desenvolvimento e as funções tireoideanas.Arq Bras Endocrinol Metab. 2010;54(6):555-9 Descritores Hipotireoidismo congênito; disgenesia da tireoide; PAX8; mutação genética

High prevalence of congenital hypothyroidism in Isfahan: Do familial components have a role?

“…[57] We hypothesize that iodine status is the main phenomic modifier of TPO function as reported by Ris-Stalpers and Bikker. [58]…”

Developmental Defects of the Thyroid Gland: Relationship with Advanced Maternal Age

“…The prevalence is higher in Hispanics and Caucasians. Mutations associated with TD (TSHR, PAX8, NKX2-1, FOXE1, NKX2-5 and PAX9) account for only 2% of all cases (1,2,9). The possible role of humoral and environmental factors or post-zygotic events in thyroid development has not been excluded (10).…”

Resistance to thyrotropin

“…Although initially associated with thyroid dysgenesis [61], PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis [62–64] but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup [65–68].…”