{"title":"【新型MYORG基因变异致原发性家族性脑钙化1例报道】。","authors":"Enkui Xia, Yixin Kang, Xiaosheng Zheng, Wei Luo","doi":"10.3760/cma.j.cn511374-202310-00143","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To investigate the clinical characteristics and genetic etiology of a primary familial brain calcification (PFBC) family, and analyze the pathogenic mechanism of MYORG gene variants.</p><p><strong>Methods: </strong>A 17-year-old female who presented to the Second Affiliated Hospital of Zhejiang University School of Medicine on 13 May 2024 with \"paroxysmal limb twitching for 1 day\" was enrolled. The patient and her parents underwent clinical evaluation and neuroimaging. Peripheral blood samples were collected for whole exome sequencing (WES). Candidate variants were confirmed by Sanger sequencing and interpreted using the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as the ACMG Guidelines). This study was approved by Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (Ethics No. 2020-674).</p><p><strong>Results: </strong>The patient experienced epileptic seizures. Cranial CT revealed multiple calcifications in the bilateral basal ganglia and cerebellum, with a total calcification score of 23. WES identified compound heterozygous variants in MYORG: c.337_348dup (p.Leu113_Arg116dup), a known pathogenic variant, and c.1268T>G (p.Val423Gly). Segregation analysis showed that the father carried the c.337_348dup heterozygous variant, whereas the mother carried the c.1268T>G heterozygous variant. According to ACMG guidelines, the c.1268T>G variant was classified as \"likely pathogenic\" (PM2_Supporting + PM3_Supporting + PP1_Supporting + PP3_Moderate + PP4_Supporting).</p><p><strong>Conclusion: </strong>The novel compound heterozygous MYORG variants c.337_348dup and c.1268T>G have broadened the mutational spectrum of the MYORG gene and further supported compound heterozygosity as an important genetic mechanism in MYORG-related PFBC.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 4","pages":"474-479"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[A case report of a family with Primary familial brain calcification caused by a novel MYORG gene variants].\",\"authors\":\"Enkui Xia, Yixin Kang, Xiaosheng Zheng, Wei Luo\",\"doi\":\"10.3760/cma.j.cn511374-202310-00143\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To investigate the clinical characteristics and genetic etiology of a primary familial brain calcification (PFBC) family, and analyze the pathogenic mechanism of MYORG gene variants.</p><p><strong>Methods: </strong>A 17-year-old female who presented to the Second Affiliated Hospital of Zhejiang University School of Medicine on 13 May 2024 with \\\"paroxysmal limb twitching for 1 day\\\" was enrolled. The patient and her parents underwent clinical evaluation and neuroimaging. Peripheral blood samples were collected for whole exome sequencing (WES). Candidate variants were confirmed by Sanger sequencing and interpreted using the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as the ACMG Guidelines). This study was approved by Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (Ethics No. 2020-674).</p><p><strong>Results: </strong>The patient experienced epileptic seizures. Cranial CT revealed multiple calcifications in the bilateral basal ganglia and cerebellum, with a total calcification score of 23. WES identified compound heterozygous variants in MYORG: c.337_348dup (p.Leu113_Arg116dup), a known pathogenic variant, and c.1268T>G (p.Val423Gly). Segregation analysis showed that the father carried the c.337_348dup heterozygous variant, whereas the mother carried the c.1268T>G heterozygous variant. According to ACMG guidelines, the c.1268T>G variant was classified as \\\"likely pathogenic\\\" (PM2_Supporting + PM3_Supporting + PP1_Supporting + PP3_Moderate + PP4_Supporting).</p><p><strong>Conclusion: </strong>The novel compound heterozygous MYORG variants c.337_348dup and c.1268T>G have broadened the mutational spectrum of the MYORG gene and further supported compound heterozygosity as an important genetic mechanism in MYORG-related PFBC.</p>\",\"PeriodicalId\":39319,\"journal\":{\"name\":\"中华医学遗传学杂志\",\"volume\":\"42 4\",\"pages\":\"474-479\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-04-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"中华医学遗传学杂志\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3760/cma.j.cn511374-202310-00143\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"中华医学遗传学杂志","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3760/cma.j.cn511374-202310-00143","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
[A case report of a family with Primary familial brain calcification caused by a novel MYORG gene variants].
Objective: To investigate the clinical characteristics and genetic etiology of a primary familial brain calcification (PFBC) family, and analyze the pathogenic mechanism of MYORG gene variants.
Methods: A 17-year-old female who presented to the Second Affiliated Hospital of Zhejiang University School of Medicine on 13 May 2024 with "paroxysmal limb twitching for 1 day" was enrolled. The patient and her parents underwent clinical evaluation and neuroimaging. Peripheral blood samples were collected for whole exome sequencing (WES). Candidate variants were confirmed by Sanger sequencing and interpreted using the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as the ACMG Guidelines). This study was approved by Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (Ethics No. 2020-674).
Results: The patient experienced epileptic seizures. Cranial CT revealed multiple calcifications in the bilateral basal ganglia and cerebellum, with a total calcification score of 23. WES identified compound heterozygous variants in MYORG: c.337_348dup (p.Leu113_Arg116dup), a known pathogenic variant, and c.1268T>G (p.Val423Gly). Segregation analysis showed that the father carried the c.337_348dup heterozygous variant, whereas the mother carried the c.1268T>G heterozygous variant. According to ACMG guidelines, the c.1268T>G variant was classified as "likely pathogenic" (PM2_Supporting + PM3_Supporting + PP1_Supporting + PP3_Moderate + PP4_Supporting).
Conclusion: The novel compound heterozygous MYORG variants c.337_348dup and c.1268T>G have broadened the mutational spectrum of the MYORG gene and further supported compound heterozygosity as an important genetic mechanism in MYORG-related PFBC.
期刊介绍:
Chinese Journal of Medical Genetics is a medical journal, founded in 1984, under the supervision of the China Association for Science and Technology, sponsored by the Chinese Medical Association (hosted by Sichuan University), and is now a monthly magazine, which attaches importance to academic orientation, adheres to the scientific, scholarly, advanced, and innovative, and has a certain degree of influence in the industry.
Chinese Journal of Medical Genetics is a journal of Peking University, and is now included in Peking University Journal (Chinese Journal of Humanities and Social Sciences), CSCD Source Journals of Chinese Science Citation Database (with extended version), Statistical Source Journals (China Science and Technology Dissertation Outstanding Journals), Zhi.com (in Chinese), Wipu (in Chinese), Wanfang (in Chinese), CA Chemical Abstracts (U.S.), JST (Japan Science and Technology Science and Technology), and JST (Japan Science and Technology Science and Technology Research Center). ), JST (Japan Science and Technology Agency), Pж (AJ) Abstracts Journal (Russia), Copernicus Index (Poland), Cambridge Scientific Abstracts, Abstracts and Citation Database, Abstracts Magazine, Medical Abstracts, and so on.