{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:02:55Z","timestamp":1789758175816,"version":"4.0.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Within the last two decades, heterozygous loss-of-function <jats:italic>PAX8<\/jats:italic> mutations have been reported in patients with a wide degree of thyroid gland dysfunction and growth despite the presence of identical mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To search for <jats:italic>PAX8<\/jats:italic> mutations in a cohort of patients with congenital hypothyroidism (CH) and various types of thyroid gland defects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>A cross-sectional study was conducted in a cohort of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>The French neonatal screening program was used for recruiting patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>A total of 118 patients with CH, including 45 with familial and 73 with sporadic diseases, were included in this study. The thyroid gland was normal in 23 patients had hypoplasia, 25 had hemithyroid agenesis, 21 had athyreosis, and 21 had ectopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found four different <jats:italic>PAX8<\/jats:italic> mutations (p.R31C, p.R31H, p.R108X, and p.I47T) in ten patients (six patients with CH and four family members), two with sporadic and eight with familial diseases. Imaging studies performed in the index cases showed ectopic thyroid gland (<jats:italic>n<\/jats:italic>=2), hypoplasia (<jats:italic>n<\/jats:italic>=2), eutopic lobar asymmetry (<jats:italic>n<\/jats:italic>=1), and eutopic gland compatible with dyshormonogenesis (<jats:italic>n<\/jats:italic>=1). The previously reported p.R31C and the novel p.I47T <jats:italic>PAX8<\/jats:italic> mutations are devoid of activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Four different <jats:italic>PAX8<\/jats:italic> mutations were detected in six index patients with CH (ten total subjects). The p.R31C, p.R31H, and p.R108X mutations have been reported. The novel p.I47T <jats:italic>PAX8<\/jats:italic> mutation presented loss of function leading to CH. Thyroid ectopy was observed in two cases of <jats:italic>PAX8<\/jats:italic> (p.R31H) mutation, a finding that has not been reported previously. We observed a high inter-individual and intra-familial variability of the phenotype in PAX8 mutations, underlining that population genetic studies for CH should include patients with various clinical presentations.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-13-1006","type":"journal-article","created":{"date-parts":[[2014,9,12]],"date-time":"2014-09-12T04:54:38Z","timestamp":1410497678000},"page":"499-507","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":41,"title":["Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations"],"prefix":"10.1093","volume":"171","author":[{"given":"H E","family":"Ramos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Carr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Chevrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Szinnai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Tron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T L O","family":"Cerqueira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"L\u00e9ger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Cabrol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Puel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Queinnec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"De Roux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Guillot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Castanet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Polak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"1","key":"1_6002775","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/1753","volume":"19","author":"Macchia","year":"1998","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"issue":"1-2","key":"2_36915252","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.mce.2010.03.009","volume":"322","author":"Montanelli","year":"2010","journal-title":"Molecular and cellular endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0303-7207","issn-type":"print"},{"key":"3_47704620","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1089\/thy.2012.0267","volume":"23","year":"2013","journal-title":"Thyroid : official journal of the American Thyroid Association","ISSN":"https:\/\/id.crossref.org\/issn\/1050-7256","issn-type":"print"},{"issue":"2","key":"4_19223984","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1002\/dvdy.20653","volume":"235","author":"Ido","year":"2006","journal-title":"Developmental dynamics : an official publication of the American Association of Anatomists","ISSN":"https:\/\/id.crossref.org\/issn\/1058-8388","issn-type":"print"},{"issue":"9","key":"5_33953409","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1590\/S0004-27302008000900003","volume":"52","author":"Ramos","year":"2008","journal-title":"Arquivos brasileiros de endocrinologia e metabologia","ISSN":"https:\/\/id.crossref.org\/issn\/0004-2730","issn-type":"print"},{"issue":"1","key":"6_18629089","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1210\/jc.2004-1358","volume":"90","year":"2005","journal-title":"Journal of Clinical Endocrinology &amp; 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