{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:43:29Z","timestamp":1787849009625,"version":"build-2784847793"},"reference-count":26,"publisher":"Walter de Gruyter GmbH","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2019-0433_abs_001_w2aab3b7c25b1b6b1aab1c15b2Aa\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Congenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2019-0433_abs_002_w2aab3b7c25b1b6b1aab1c15b3Aa\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2019-0433_abs_003_w2aab3b7c25b1b6b1aab1c15b4Aa\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified potentially pathogenic bi-allelic variants in <jats:italic>DUOX2<\/jats:italic>, <jats:italic>TSHR<\/jats:italic>, and <jats:italic>TPO<\/jats:italic> in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in <jats:italic>NKX2-1<\/jats:italic> (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (<jats:italic>DUOX2<\/jats:italic>, <jats:italic>TSHR<\/jats:italic>, <jats:italic>TG<\/jats:italic>, <jats:italic>DUOXA2<\/jats:italic>, and <jats:italic>TPO<\/jats:italic>) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic <jats:italic>DUOX2<\/jats:italic> variants showed a more severe clinical presentation in infancy than those with bi-allelic <jats:italic>TSHR<\/jats:italic> variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic <jats:italic>DUOX2<\/jats:italic> variants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2019-0433_abs_004_w2aab3b7c25b1b6b1aab1c15b5Aa\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2019-0433","type":"journal-article","created":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T10:33:28Z","timestamp":1590748408000},"page":"691-701","source":"Crossref","is-referenced-by-count":22,"title":["Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism"],"prefix":"10.1515","volume":"33","author":[{"given":"Tatsushi","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Neonatology , Nagoya City University , Graduate School of Medical Sciences , Nagoya , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Aoyama","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neonatology , Nagoya City University , Graduate School of Medical Sciences , Nagoya , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neonatology , Nagoya City University , Graduate School of Medical Sciences , Nagoya , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Saitoh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neonatology , Nagoya City University , Graduate School of Medical Sciences , Nagoya , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruo","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Fujita Health University School of Medicine , 1-98 Dengakugakubo , Kutsukake-cho , Toyoake , Aichi, 470-1192 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2020,5,29]]},"reference":[{"key":"2023040101344796767_j_jpem-2019-0433_ref_001_w2aab3b7c25b1b6b1ab2b2b1Aa","doi-asserted-by":"crossref","unstructured":"Ford G, LaFranchi SH. 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