{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:21:13Z","timestamp":1790014873477,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,3,21]],"date-time":"2020-03-21T00:00:00Z","timestamp":1584748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin City","doi-asserted-by":"publisher","award":["16JCQNJC11900"],"award-info":[{"award-number":["16JCQNJC11900"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771589"],"award-info":[{"award-number":["81771589"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cobalamin (cbl) C is a treatable rare hereditary disorder of cbl metabolism with autosomal recessive inheritance. It is the most common organic acidemia, manifested as methylmalonic academia combined with homocysteinemia. Early screening and diagnosis are important. The mutation spectrum of the <jats:italic>MMACHC<\/jats:italic> gene causing cblC varies among populations. The mutation spectrum in Chinese population is notably different from that in other populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A PCR followed by high\u2010resolution melting curve analysis (PCR\u2010HRM) method covering all coding exons of <jats:italic>MMACHC<\/jats:italic> gene was designed to verify 14 pathogenic <jats:italic>MMACHC<\/jats:italic> gene variants found in patients with cblC, including all common mutations in Chinese patients with cblC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>By PCR\u2010HRM analysis, 14 pathogenic variants of <jats:italic>MMACHC<\/jats:italic> showed distinctly different melting curves, which were consistent with Sanger sequencing. The homozygous type of the most common mutation c.609G\u00a0&gt;\u00a0A (p.Trp203Ter) can also be analyzed by specially designed PCR\u2010HRM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The established PCR\u2010HRM method for screening common pathogenic <jats:italic>MMACHC<\/jats:italic> variants in Chinese patients with cblC has the advantages of high accuracy, high throughput, low cost, and high speed. It is suitable for the large\u2010sample screening of suspected children with methylmalonic acidemia and carriers in population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1221","type":"journal-article","created":{"date-parts":[[2020,3,21]],"date-time":"2020-03-21T09:24:09Z","timestamp":1584782649000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Rapid screening of <i>MMACHC<\/i> gene mutations by high\u2010resolution melting curve analysis"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9423-6502","authenticated-orcid":false,"given":"Chao","family":"Wang","sequence":"first","affiliation":[{"name":"Tianjin Pediatric Research Institute Tianjin Children\u2019s Hospital Tianjin China"},{"name":"Tianjin Key Laboratory of Prevention and Treatment of Birth Defects Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neonatalogy Tianjin Children\u2019s Hospital The Pediatric Clinical College in Tianjin Medical University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengying","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Physiology Tianjin Medical College Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Pediatric Research Institute Tianjin Children\u2019s Hospital Tianjin China"},{"name":"Tianjin Key Laboratory of Prevention and Treatment of Birth Defects Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Xu","sequence":"additional","affiliation":[{"name":"Tianjin Pediatric Research Institute Tianjin Children\u2019s Hospital Tianjin China"},{"name":"Tianjin Key Laboratory of Prevention and Treatment of Birth Defects Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yani","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Quyang County People's Hospital Baoding China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Tianjin Children\u2019s Hospital Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Tianjin Children\u2019s Hospital Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Children\u2019s Hospital Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Respiration Tianjin Children\u2019s Hospital Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunquan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Tianjin Children\u2019s Hospital Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5903-7954","authenticated-orcid":false,"given":"Jianbo","family":"Shu","sequence":"additional","affiliation":[{"name":"Tianjin Pediatric Research Institute Tianjin Children\u2019s Hospital Tianjin China"},{"name":"Tianjin Key Laboratory of Prevention and Treatment of Birth Defects Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1393-1"},{"issue":"4","key":"e_1_2_8_3_1","first-page":"507","article-title":"Rapid screening for targeted genetic variants via high\u2010resolution melting curve analysis","volume":"55","author":"Chambliss A. 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