{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:06:53Z","timestamp":1793196413573,"version":"4.5.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the Major Science and Technology Program of Hainan Province","award":["ZDKJ2021037"],"award-info":[{"award-number":["ZDKJ2021037"]}]},{"name":"Hainan Province Science and Technology Special Fund","award":["ZDYF2020117, ZDYF2022SHFZ312"],"award-info":[{"award-number":["ZDYF2020117, ZDYF2022SHFZ312"]}]},{"name":"Hainan Province Science and Technology Project","award":["LCXY202102, LCYX202203, LCYX202301"],"award-info":[{"award-number":["LCXY202102, LCYX202203, LCYX202301"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pregnancy Childbirth"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Ornithine carbamoyltransferase deficiency (OTCD) is a kind of X-linked metabolic disease caused by a deficiency in ornithine transcarbamylase leading to urea cycle disorders. The main reason is that the <jats:italic>OTC<\/jats:italic> gene variants lead to the loss or decrease of <jats:italic>OTC<\/jats:italic> enzyme function, which hinders the ammonia conversion to urea, resulting in hyperammonemia and severe neurological dysfunction. Here, we studied one Chinese family of three generations who consecutively gave birth to two babies with OTCD. This study aims to explore the pathogenicity of two missense variants in the <jats:italic>OTC<\/jats:italic> gene and investigate the application of preimplantation genetic testing for monogenic (PGT-M) for a family troubled by Ornithine carbamoyltransferase deficiency (OTCD).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The retrospective method was used to classify the pathogenicity of two missense variants in the <jats:italic>OTC<\/jats:italic> gene in a family tortured by OTCD. Sanger sequencing was used to validate the variants in the <jats:italic>OTC<\/jats:italic> gene, and then the pathogenicity of variants was confirmed through family analysis and bioinformatics software. We used PGT-M to target the <jats:italic>OTC<\/jats:italic> gene and select a suitable embryo for transplantation. Prenatal diagnosis was recommended to confirm previous results using Sanger sequencing and karyotyping at an appropriate gestational stage. Tandem mass spectrometry (MS-MS) and gas chromatography-mass spectrometry (GC-MS) were used to detect fetal metabolism after birth. The number of the study cohort is ChiCTR2100053616.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Two missense variants, c.959G\u2009&gt;\u2009C (p.Arg320Pro) and c.634G\u2009&gt;\u2009A (p.Gly212Arg), were validated in the <jats:italic>OTC<\/jats:italic> gene in this family. According to the ACMG genetic variation classification criteria, the missense variant c.959G\u2009&gt;\u2009C can be considered as \u201cpathogenic\u201d, and the missense variant c.634G\u2009&gt;\u2009A can be regarded as \u201clikely benign.\u201d PGT-M identified a female embryo carrying the heterozygous variant c.959G\u2009&gt;\u2009C (p.Arg320Pro), which was selected for transplantation. Prenatal diagnosis revealed the same variant in the fetus, and continued pregnancy was recommended. A female baby was born, and her blood amino acid testing and urine organic acid testing were regular. Follow-up was conducted after six months and indicated the girl was healthy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our research first validated the segregation of both c.959G\u2009&gt;\u2009C and c.634G\u2009&gt;\u2009A variants in the <jats:italic>OTC<\/jats:italic> gene in a Chinese OTCD family. Then, we classified variant c.959G\u2009&gt;\u2009C as \u201cpathogenic\u201d and variant c.634G\u2009&gt;\u2009A as \u201clikely benign\u201d, providing corresponding theoretical support for genetic counseling and fertility guidance in this family. PGT-M and prenatal diagnosis were recommended to help the couple receive a female baby successfully with a six-month follow-up.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12884-024-06696-5","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T08:01:54Z","timestamp":1721635314000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Variant analysis and PGT-M of OTC gene in a Chinese family with ornithine carbamoyltransferase deficiency"],"prefix":"10.1186","volume":"24","author":[{"given":"Yao","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxing","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"key":"6696_CR1","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/S0065-3101(24)00072-0","volume":"43","author":"SW Brusilow","year":"1996","unstructured":"Brusilow SW, Maestri NE. Urea cycle disorders: diagnosis, pathophysiology, and therapy [J]. Adv Pediatr. 1996;43:127\u201370.","journal-title":"Adv Pediatr"},{"issue":"5","key":"6696_CR2","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.jgg.2015.04.003","volume":"42","author":"L Caldovie","year":"2015","unstructured":"Caldovie L, Abdikarim I, Narain S, et al. Genotype-pheno-type corrdations in arnithine transcarhamylase deficieney:Amutation update [J]. J Genet Gencmics. 2015;42(5):181\u201394.","journal-title":"J Genet Gencmics"},{"issue":"6","key":"6696_CR3","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1177\/0883073814535490","volume":"30","author":"P Prasun","year":"2015","unstructured":"Prasun P, Alinok D, Misra VK. Ornithine transcarbamylase deficiency presenting with aute reversible corial blind-ness [J]. 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