{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:24:03Z","timestamp":1789539843205,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T00:00:00Z","timestamp":1521936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY002162"],"award-info":[{"award-number":["EY002162"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>Congenital sodium diarrhea is a rare and life\u2010threatening disorder characterized by a severe, secretory diarrhea containing high concentrations of sodium, leading to hyponatremia and metabolic acidosis. It may occur in isolation or in association with systemic features such as facial dysmorphism, choanal atresia, imperforate anus, and corneal erosions. Mutations in the serine protease inhibitor, Kunitz\u2010Type 2 (<jats:italic>SPINT2<\/jats:italic>) gene have been associated with congenital sodium diarrhea and additional syndromic features. We present a child with congenital sodium diarrhea, cleft lip and palate, corneal erosions, optic nerve coloboma, and intermittent exotropia who was found to have biallelic mutations in <jats:italic>SPINT2<\/jats:italic>. One mutation, c.488A\u2009&gt;\u2009G, predicting p.(Tyr163Cys), has been previously associated with a syndromic form of congenital sodium diarrhea. The other mutation, c.166_167dupTA, predicting p.(Asn57Thrfs*24) has not previously been reported and is likely a novel pathogenic variant for this disorder. We found only one other report of an optic nerve coloboma associated with <jats:italic>SPINT2<\/jats:italic> mutations and this occurred in a patient with congenital tufting enteropathy. Our patient confirms an association of ocular coloboma with presumed loss of SPINT2 function.<\/jats:p>","DOI":"10.1002\/ajmg.a.38637","type":"journal-article","created":{"date-parts":[[2018,4,6]],"date-time":"2018-04-06T03:36:53Z","timestamp":1522985813000},"page":"997-1000","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Congenital sodium diarrhea and chorioretinal coloboma with optic disc coloboma in a patient with biallelic SPINT2 mutations, including p.(Tyr163Cys)"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6518-3640","authenticated-orcid":false,"given":"Kristin E.","family":"Hirabayashi","sequence":"first","affiliation":[{"name":"Department of Ophthalmology University of California, San Francisco San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony T.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of California, San Francisco San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce A.","family":"Mendelsohn","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pediatrics University of California, San Francisco San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan J.","family":"Taft","sequence":"additional","affiliation":[{"name":"Clinical Genomics Research, Illumina Inc. San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Chawla","sequence":"additional","affiliation":[{"name":"Clinical Genomics Research, Illumina Inc. San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Perry","sequence":"additional","affiliation":[{"name":"Clinical Genomics Research, Illumina Inc. San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan","family":"Henry","sequence":"additional","affiliation":[{"name":"Division of Critical Care, Department of Pediatrics University of California, San Francisco San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Slavotinek","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pediatrics University of California, San Francisco San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,25]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-015-0070-y"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094267"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.01.004"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1597\/09-217"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.44.27558"},{"key":"e_1_2_5_7_1","first-page":"192872","article-title":"Strelka2: Fast and accurate variant calling for clinical sequencing applications","author":"Kim S.","year":"2017","journal-title":"bioRxiv"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.20514"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)01105-3"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt314"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw163"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1380-6"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts271"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e328331de38"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e328361d42f"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.038430"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.137968"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.38637","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38637","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.38637","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38637","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T13:42:37Z","timestamp":1693230157000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,25]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1002\/ajmg.a.38637"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38637","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,25]]},"assertion":[{"value":"2017-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}