{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:47:05Z","timestamp":1789516025840,"version":"build-2803163510"},"reference-count":29,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seed for Research Contest 2013","award":["2013"],"award-info":[{"award-number":["2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Congenital thyroid dyshormonogenesis is caused by alterations in the synthesis of thyroid hormones in a newborn. Additionally, 10 to 20% of these cases are hereditary, caused by defects in proteins involved in hormonal synthesis. One of the most common causes is mutations in the thyroid peroxidase (TPO) enzyme gene, an autosomal recessive disease. We aimed to detect mutations of the TPO gene in 12 Chilean patients with congenital hypothyroidism due to dyshormonogenesis (CHD) and to characterize these patients clinically and molecularly. Materials and Methods: Twelve patients under 20 years of age with CHD, controlled at San Juan de Dios Hospital in Santiago, Chile, were selected according to the inclusion criteria: elevated neonatal TSH, persistent hypothyroidism, and thyroid normotopic by imaging study. Those with deafness, Down syndrome, and central or transient congenital hypothyroidism were excluded. Blood samples were taken for DNA extraction, and the 17 exons and exon\u2013intron junctions of the TPO gene were amplified by PCR. The PCR products were sequenced by Sanger. Results: Two possibly pathogenic mutations of the TPO gene were detected: c.2242G&gt;A (p.Val748Met) and c.1103C&gt;T (p.Pro368Leu). These mutations were detected in 2 of 12 patients (16.6%): 1 was compound heterozygous c.1103C&gt;T\/c.2242G&gt;A, and the other was heterozygous for c.2242G&gt;A. In the diagnostic confirmation test, both patients presented diffuse hyper-uptake goiter on thyroid scintigraphy and high TSH in venous blood (&gt;190 uIU\/mL). Conclusions: The frequency of patients with possibly pathogenic mutations in TPO with CHD was 16.6%. Its study would allow for genetic counseling to be offered to the families of affected patients.<\/jats:p>","DOI":"10.3390\/medicina60071145","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T15:05:51Z","timestamp":1721142351000},"page":"1145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Frequency of Mutations in the TPO Gene in Patients with Congenital Hypothyroidism Due to Dyshormonogenesis in Chile"],"prefix":"10.3390","volume":"60","author":[{"given":"Mar\u00eda Clara","family":"Arteaga-Jacobo","sequence":"first","affiliation":[{"name":"Programa de Gen\u00e9tica Humana, Institute of Biomedical Science (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8850-1018","authenticated-orcid":false,"given":"\u00c1ngel","family":"Roco-Videla","sequence":"additional","affiliation":[{"name":"Vicerectoria de Investigaci\u00f3n e Innovaci\u00f3n, Universidad Arturo Prat, Iquique 1110939, Chile"},{"name":"Facultad de Medicina, Universidad Cat\u00f3lica de la Sant\u00edsima Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Villota Arcos","sequence":"additional","affiliation":[{"name":"Escuela de Nutrici\u00f3n y Diet\u00e9tica, Facultad de Ciencias de la Salud, Universidad Bernardo O\u2019Higgins, Santiago 8370993, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio","family":"Gonz\u00e1lez-Hormaz\u00e1bal","sequence":"additional","affiliation":[{"name":"Programa de Gen\u00e9tica Humana, Institute of Biomedical Science (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Gonzalo-Castro","sequence":"additional","affiliation":[{"name":"Programa de Gen\u00e9tica Humana, Institute of Biomedical Science (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Virginia","family":"P\u00e9rez-Flores","sequence":"additional","affiliation":[{"name":"Hospital San Juan de Dios, Santiago 8350488, Chile"},{"name":"Hospital Luis Calvo Mackenna, Santiago 7500539, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1750-1172-5-17","article-title":"Congenital Hypothyroidism","volume":"5","author":"Rastogi","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1210\/jc.2013-1891","article-title":"European Society for Paediatric Endocrinology Consensus Guidelines on Screening, Diagnosis, and Management of Congenital Hypothyroidism","volume":"99","author":"Olivieri","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0083-6729(05)71004-9","article-title":"Thyroid Hormones and Brain Development","volume":"Volume 71","author":"Litwack","year":"2005","journal-title":"Vitamins & Hormones"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s10545-010-9165-8","article-title":"Past, Present and Future of Newborn Screening in Chile","volume":"33","author":"Cornejo","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1159\/000363156","article-title":"Clinical Genetics of Congenital Hypothyroidism","volume":"Volume 26","author":"Szinnai","year":"2014","journal-title":"Endocrine Development"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.mce.2010.01.029","article-title":"Defects of Thyroidal Hydrogen Peroxide Generation in Congenital Hypothyroidism","volume":"322","author":"Grasberger","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/cen.12127","article-title":"Thyroid Dyshormonogenesis Is Mainly Caused TPO Mutations in Consanguineous Community","volume":"79","author":"Cangul","year":"2013","journal-title":"Clin. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s42000-020-00267-x","article-title":"Genetics of Primary Congenital Hypothyroidism\u2014A Review","volume":"20","author":"Kostopoulou","year":"2021","journal-title":"Hormones"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1515\/jpem-2019-0433","article-title":"Clinical and Genetic Investigation of 136 Japanese Patients with Congenital Hypothyroidism","volume":"33","author":"Tanaka","year":"2020","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_10","first-page":"297","article-title":"Mutation Spectrum Analysis of 29 Causative Genes in 43 Chinese Patients with Congenital Hypothyroidism","volume":"22","author":"Wang","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1046\/j.1365-2265.1999.00746.x","article-title":"A Novel Mutation in the TPO Gene in Goitrous Hypothyroid Patients with Iodide Organification Defect","volume":"51","author":"Santos","year":"1999","journal-title":"Clin. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1677\/joe.0.1720627","article-title":"Mutation Analysis of Thyroid Peroxidase Gene in Chinese Patients with Total Iodide Organification Defect: Identification of Five Novel Mutations","volume":"172","author":"Wu","year":"2002","journal-title":"J. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nprot.2006.83","article-title":"The Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate-Phenol-Chloroform Extraction: Twenty-Something Years On","volume":"1","author":"Chomczynski","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"717283","DOI":"10.1155\/2012\/717283","article-title":"Thyroid Peroxidase Gene Mutation in Patients with Congenital Hypothyroidism in Isfahan, Iran","volume":"2012","author":"Hashemipour","year":"2012","journal-title":"Int. J. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s12020-022-03054-3","article-title":"Mutational Screening of the TPO and DUOX2 Genes in Argentinian Children with Congenital Hypothyroidism Due to Thyroid Dyshormonogenesis","volume":"77","author":"Molina","year":"2022","journal-title":"Endocrine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110761","DOI":"10.1016\/j.mce.2020.110761","article-title":"The TPO Mutation Screening and Genotype-Phenotype Analysis in 230 Chinese Patients with Congenital Hypothyroidism","volume":"506","author":"Zhang","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Garcia, F.A.D.O., Andrade, E.S.D., and Palmero, E.I. (2022). Insights on Variant Analysis in Silico Tools for Pathogenicity Prediction. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.1010327"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.gim.2021.11.018","article-title":"Evaluating the Impact of in Silico Predictors on Clinical Variant Classification","volume":"24","author":"Wilcox","year":"2022","journal-title":"Genet. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1210\/jc.2002-021377","article-title":"Monoallelic Expression of Mutant Thyroid Peroxidase Allele Causing Total Iodide Organification Defect","volume":"88","author":"Fugazzola","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.1365-2265.2007.02869.x","article-title":"Two Compound Heterozygous Mutations (c.215delA\/c.2422T\u2192C and c.387delC\/c.1159G\u2192A) in the Thyroid Peroxidase Gene Responsible for Congenital Goitre and Iodide Organification Defect","volume":"67","author":"Rivolta","year":"2007","journal-title":"Clin. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1590\/S0004-27302010000800012","article-title":"Monoallelic Thyroid Peroxidase Gene Mutation in a Patient with Congenital Hypothyroidism with Total Iodide Organification Defect","volume":"54","author":"Neves","year":"2010","journal-title":"Arq. Bras. Endocrinol. Metabol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.arcmed.2012.01.011","article-title":"Targeted Next Generation Sequencing Reveals a Novel Intragenic Deletion of the TPO Gene in a Family with Intellectual Disability","volume":"43","author":"Iqbal","year":"2012","journal-title":"Arch. Med. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1530\/eje.1.01826","article-title":"Mutation Screening of the Thyroid Peroxidase Gene in a Cohort of 55 Portuguese Patients with Congenital Hypothyroidism","volume":"152","author":"Rodrigues","year":"2005","journal-title":"Eur. J. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/j.1365-2265.2011.04249.x","article-title":"Congenital Goitrous Hypothyroidism: Mutation Analysis in the Thyroid Peroxidase Gene","volume":"76","author":"Belforte","year":"2012","journal-title":"Clin. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1530\/eje.0.1450019","article-title":"Novel Mutations of the Thyroid Peroxidase Gene in Patients with Permanent Congenital Hypothyroidism","volume":"145","author":"Ambrugger","year":"2001","journal-title":"Eur. J. Endocrinol."},{"key":"ref_27","first-page":"283","article-title":"Cintigraf\u00eda Tiroidea (CT) Con Tc99m- Pertecnectato En Reci\u00e9n Nacidos (RN) Con Hipotiroidismo Cong\u00e9nito (HC)","volume":"131","year":"2003","journal-title":"Rev. M\u00e9dica Chile"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.mce.2010.02.008","article-title":"Genetics and Phenomics of Hypothyroidism and Goiter Due to TPO Mutations","volume":"322","author":"Bikker","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E1838","DOI":"10.1210\/jc.2011-1573","article-title":"Molecular Basis of Thyroid Dyshormonogenesis: Genetic Screening in Population-Based Japanese Patients","volume":"96","author":"Narumi","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/7\/1145\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:17:44Z","timestamp":1760109464000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/7\/1145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,16]]},"references-count":29,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["medicina60071145"],"URL":"https:\/\/doi.org\/10.3390\/medicina60071145","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,16]]}}}