{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T10:43:44Z","timestamp":1793357024227,"version":"4.5.0"},"reference-count":11,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Biallelic pathogenic variants in the <jats:italic>KCNJ16<\/jats:italic> gene result in hypokalemic tubulopathy and deafness (HKTD) (MIM #619406), which is a rare autosomal recessive disease characterized by hypokalemic tubulopathy with renal salt wasting, disturbed acid\u2013base homeostasis, and sensorineural deafness. Currently, nine individuals with HKTD have been reported, and seven pathogenic variants in <jats:italic>KCNJ16<\/jats:italic> have been revealed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 5\u2010year\u20106\u2010month\u2010old Chinese female patient displayed hypokalemic metabolic acidosis, salt wasting, renin\u2010angiotensin\u2010aldosterone system (RAAS) activation, arrhythmia, myocardial damage, cardiogenic shock and secondary diffuse brain oedema. Trio\u2010based whole\u2010exome sequencing (WES) was applied to detect the genetic cause.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Novel compound heterozygous variants, c.190A&gt;C (p.Thr64Pro) and c.628C&gt;G (p.His210Asp), in <jats:italic>KCNJ16<\/jats:italic> were detected in the patient, and these variants were inherited from the patient's mother and father, respectively. Then, we systematically reviewed the available clinical manifestations of individuals with HKTD. We found that HKTD patients are at risk of cardiogenic shock and secondary diffuse brain oedema, which urges clinicians to make early diagnoses with prompt treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings expand the variant spectrum of <jats:italic>KCNJ16<\/jats:italic>, enrich the clinical characteristics of HKTD, and provide a solid base for the genetic counseling, diagnosis and treatment of this condition.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2238","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T13:50:16Z","timestamp":1689774616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Novel <scp><i>KCNJ16<\/i><\/scp> variants identified in a Chinese patient with hypokalemic metabolic acidosis"],"prefix":"10.1002","volume":"11","author":[{"given":"Jianxiong","family":"Chen","sequence":"first","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital  Dongguan China"},{"name":"Key Laboratory for Precision Diagnosis and Treatment of Severe Infectious Diseases in Children  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youqing","family":"Fu","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital  Dongguan China"},{"name":"Key Laboratory for Precision Diagnosis and Treatment of Severe Infectious Diseases in Children  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingming","family":"Wang","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital  Dongguan China"},{"name":"Department of Medical Genetics Dongguan Maternal and Child Health Care Hospital  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Li","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8510-0419","authenticated-orcid":false,"given":"Haiming","family":"Yuan","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital  Dongguan China"},{"name":"Department of Medical Genetics Dongguan Maternal and Child Health Care Hospital  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.189290"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02202-5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000015662"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.012961"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000437"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020111587"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00587.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000248"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00883-0"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2020.03.006"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2238","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T03:47:03Z","timestamp":1700279223000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,19]]},"references-count":11,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1002\/mgg3.2238"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2238","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,19]]},"assertion":[{"value":"2023-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2238"}}