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dc.contributor.authorCongdon, Tamara
dc.contributor.authorNguyen, Lynda Q.
dc.contributor.authorNogueira, Celia R. [UNESP]
dc.contributor.authorHabiby, Reema L.
dc.contributor.authorMedeiros-Neto, Geraldo
dc.contributor.authorKopp, Peter
dc.date.accessioned2022-04-28T19:55:16Z
dc.date.available2022-04-28T19:55:16Z
dc.date.issued2001-01-01
dc.identifierhttp://dx.doi.org/10.1210/jcem.86.8.7765
dc.identifier.citationJournal of Clinical Endocrinology and Metabolism, v. 86, n. 8, p. 3962-3967, 2001.
dc.identifier.issn0021-972X
dc.identifier.urihttp://hdl.handle.net/11449/224201
dc.description.abstractCongenital hypothyroidism associated with thyroid hypoplasia can be caused by several genetic defects, including mutations in the TSHβ-subunit, the TSH receptor, the Gsα-subunit, and the transcription factor PAX8. Four girls with sporadic congenital hypothyroidism and hypoplastic thyroid glands were analyzed for mutations in PAX8 and TTF2 (FKHL15). Mutations in the coding region of the TSHβ-subunit gene, the TSH receptor gene, and exons 8 and 9 of Gsα had been excluded previously. Serum TSH concentrations were 150 mU/liter or more, TG levels were within normal limits, and thyroid auto-antibodies were absent. Technetium scintigraphies did not reveal the presence of thyroid tissue, but ultrasonography documented hypoplastic, normally located glands. One patient was found to harbor a heterozygous transversion 119A→C in exon 3 of PAX8 replacing a conserved glutamine by proline in the paired box domain (Q40P). Analysis of her family members revealed that her mother, who has a thyroid gland of normal size and mild, adult-onset autoimmune hypothyroidism, is also heterozygous for this mutation. Functional analyses of the PAX8 Q40P mutation showed impaired binding to a PAX8 response element and absent transactivation of a thyroid peroxidase promoter luciferase reporter gene. These findings confirm the important role of PAX8 in the development of the thyroid, but they indicate that PAX8 gene mutations may have a variable penetrance or expressivity. The absence of mutations in the coding sequences of the analyzed genes in the three other patients supports the concept that the pathogenesis of congenital hypothyroidism associated with thyroid hypoplasia is diverse.en
dc.format.extent3962-3967
dc.language.isoeng
dc.relation.ispartofJournal of Clinical Endocrinology and Metabolism
dc.sourceScopus
dc.titleA novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: Evidence for phenotypic variability in mother and childen
dc.typeArtigo
dc.contributor.institutionNorthwestern University
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.description.affiliationDivision of Endocrinology Metabolism and Molecular Medicine Northwestern University, Chicago, IL 60611
dc.description.affiliationPediatric Endocrinology Northwestern University, Chicago, IL 60611
dc.description.affiliationLaboratorio Molecular de Tiroide (LIM-25) Hospital das Clinicas Universidade de São Paulo, Sao Paulo
dc.description.affiliationDepartamento de Clinica Médica Disciplina de Endocrinologia Faculdade de Medicina UNESP, Botucatu
dc.description.affiliationDivision of Endocrinology Metabolism and Molecular Medicine Northwestern University, Tarry 15, 303 East Chicago Avenue, Chicago, IL 60611
dc.description.affiliationUnespDepartamento de Clinica Médica Disciplina de Endocrinologia Faculdade de Medicina UNESP, Botucatu
dc.identifier.doi10.1210/jcem.86.8.7765
dc.identifier.scopus2-s2.0-0034885770
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