{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T06:21:53Z","timestamp":1777875713972,"version":"3.51.4"},"reference-count":8,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:p>\n                    Iodide transport defect (ITD) is an autosomal recessive disorder caused by deficient iodide accumulation into the thyroid follicular cell. ITD is an uncommon cause of dyshormonogenetic congenital hypothyroidism that results from inactivating mutations in the sodium\/iodide symporter (NIS)-coding\n                    <jats:italic toggle=\"yes\">SLC5A5<\/jats:italic>\n                    gene. NIS is a key basolateral plasma membrane glycoprotein that efficiently mediates active iodide uptake in the thyroid\u2014constituting the first step in the biosynthesis of the iodine-containing thyroid hormones\u2014and other tissues, including salivary glands, lactating breast, and small intestine. The proposita, a 20-day-old female born in 1992, was diagnosed with congenital hypothyroidism through newborn screening. ITD was suspected on the basis of nondetectable radioiodide accumulation in a normally located nongoitrous thyroid gland, as well as in salivary glands. Sanger sequencing revealed nonpreviously reported compound heterozygous missense\n                    <jats:italic toggle=\"yes\">SLC5A5<\/jats:italic>\n                    gene variants (c.991G&gt;A, p.D331N and c.1.641C&gt;A, p.S547R). Notably, these variants have not been reported in public databases (i.e., Exome Aggregation Consortium, 1000 Genomes, and Single Nucleotide Polymorphism).\n                    <jats:italic toggle=\"yes\">In silico<\/jats:italic>\n                    analysis using prediction softwares (i.e., SIFT, Polyphen-2, and MutationTaster2) support the pathologic significance of p.D331N and p.S547R NIS. Moreover, functional\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    studies demonstrate that D331N and S547R NIS severely reduce iodide uptake when the proteins are heterologously expressed in HEK-293T cells because of a pronounced impairment of D331N and S547R NIS targeting to the plasma membrane. Of note, a charged residue at position 331 and a serine residue at position 547\u2014which are highly conserved in SLC5A family members\u2014are required for NIS plasma membrane targeting. We report two novel missense pathogenic variants in a compound heterozygous state in the\n                    <jats:italic toggle=\"yes\">SLC5A5<\/jats:italic>\n                    gene, detected through Sanger sequencing, in a pediatric female patient with dyshormonogenic congenital hypothyroidism.\n                  <\/jats:p>","DOI":"10.1089\/thy.2019.0046","type":"journal-article","created":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T07:08:56Z","timestamp":1558508936000},"page":"1023-1026","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Novel Sodium\/Iodide Symporter Compound Heterozygous Pathogenic Variants Causing Dyshormonogenic Congenital Hypothyroidism"],"prefix":"10.1177","volume":"29","author":[{"given":"Mariano","family":"Mart\u00edn","sequence":"first","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, C\u00f3rdoba, Argentina."},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos Eduardo","family":"Bernal Barquero","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, C\u00f3rdoba, Argentina."},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina Celeste","family":"Geysels","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, C\u00f3rdoba, Argentina."},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Papendieck","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas Dr. C\u00e9sar Bergad\u00e1\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires, Argentina."},{"name":"Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Dr. Ricardo Guti\u00e9rrez, Buenos Aires, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Peyret","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, C\u00f3rdoba, Argentina."},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Mar\u00eda","family":"Masini-Repiso","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, C\u00f3rdoba, Argentina."},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Elena","family":"Chiesa","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas Dr. C\u00e9sar Bergad\u00e1\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires, Argentina."},{"name":"Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Dr. Ricardo Guti\u00e9rrez, Buenos Aires, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Pablo","family":"Nicola","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, C\u00f3rdoba, Argentina."},{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,7,17]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2018.0137"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1607231113"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/js.2018-00100"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1824"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00603"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1192"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000446496"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-229138"}],"container-title":["Thyroid\u00ae"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/thy.2019.0046","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2019.0046","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2019.0046","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:05:50Z","timestamp":1777586750000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/thy.2019.0046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7]]},"references-count":8,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,7]]}},"alternative-id":["10.1089\/thy.2019.0046"],"URL":"https:\/\/doi.org\/10.1089\/thy.2019.0046","relation":{},"ISSN":["1050-7256","1557-9077"],"issn-type":[{"value":"1050-7256","type":"print"},{"value":"1557-9077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7]]}}}