{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T02:07:02Z","timestamp":1781143622961,"version":"3.54.1"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T00:00:00Z","timestamp":1595289600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T00:00:00Z","timestamp":1595289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"MINIATURA 2 Grant of Polish National Center for Science","award":["2018\/02\/X\/NZ5\/00759"],"award-info":[{"award-number":["2018\/02\/X\/NZ5\/00759"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Endocrine"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Thyroid hemiagenesis (THA) is an inborn absence of one thyroid lobe of largely unknown etiopathogenesis, affecting 0.05\u20130.5% population. The aim of the study was an identification of genetic factors responsible for thyroid maldevelopment in two siblings with THA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We evaluated a three-generation THA family with two sisters presenting the disorder. Proband (Patient II:3) was diagnosed at the age of 45 due to neck asymmetry. Left lobe agenesis and nontoxic multinodular goiter were depicted. Proband\u2019s sister (Patient II:6) was euthyroid, showed up at the age of 39 due to neck discomfort and left-sided THA was demonstrated. Affected individuals were subjected to whole-exome sequencing (WES) (Illumina, TruSeq Exome Kit) and all identified variants were evaluated for pathogenicity. Sanger sequencing was used to confirm WES data and check segregation among first-degree relatives.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In both siblings, a compound heterozygous mutations NM_000168.6: c.[2179G&gt;A];[4039C&gt;A] (NP_000159.3: p.[Gly727Arg];[Gln1347Lys]) were identified in the <jats:italic>GLI3<\/jats:italic> gene, affecting exon 14 and 15, respectively. According to the American College of Medical Genetics, variants are classified as of uncertain significance, and were found to be very rare (GnomAD MAF 0.007131 and 0.00003187). The segregation mapping and analysis of relatives indicated causativeness of compound heterozygosity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We demonstrated for the first time a unique association of THA phenotype and the presence of compound heterozygous mutations p.[Gly727Arg];[Gln1347Lys] of <jats:italic>GLI3<\/jats:italic> gene in two siblings.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12020-020-02422-1","type":"journal-article","created":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T13:04:59Z","timestamp":1595336699000},"page":"514-519","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Compound heterozygous GLI3 variants in siblings with thyroid hemiagenesis"],"prefix":"10.1007","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3661-3274","authenticated-orcid":false,"given":"Ewelina","family":"Szczepanek-Parulska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart\u0142omiej","family":"Budny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyna","family":"Borowczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Zawadzka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Sztromwasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Rucha\u0142a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"issue":"9","key":"2422_CR1","doi-asserted-by":"publisher","first-page":"3124","DOI":"10.1210\/jc.2017-00784","volume":"102","author":"E Szczepanek-Parulska","year":"2017","unstructured":"E. Szczepanek-Parulska, A. Zybek-Kocik, L. Wartofsky, M. Ruchala, Thyroid hemiagenesis: incidence, clinical significance, and genetic background. J Clin Endocrinol Metab 102(9), 3124\u20133137 (2017). https:\/\/doi.org\/10.1210\/jc.2017-00784","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2422_CR2","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s00005-016-0393-y","volume":"64","author":"E Szczepanek-Parulska","year":"2016","unstructured":"E. Szczepanek-Parulska, A. Zybek-Kocik, K. Wolinski, B. Czarnocka, M. Ruchala, T.S.H. Does, Trigger the anti-thyroid autoimmune processes? Observation on a large cohort of naive patients with thyroid hemiagenesis. 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Bioethical Committee of Poznan University of Medical Sciences approved the study (approval number 524\/18).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}