{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T21:27:48Z","timestamp":1760909268376,"version":"3.41.2"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>External ophthalmoplegia with rib and vertebral anomalies (EORVA) is characterized by congenital nonprogressive external ophthalmoplegia, ptosis, scoliosis, torticollis, vertebral, and rib anomalies, caused by homozygous mutations in the myogenic factor 5 gene (<jats:italic>MYF5<\/jats:italic>) located on chromosome 12q21.31. Uniparental disomy (UPD) is a rare inheritance of a pair of chromosomes originating from only one parent. This study describes a case of an 8-year-old boy with ptosis, scoliosis, and dysmorphic hypoplastic ribs with fusion anomalies. Trio-based exome sequencing (trio-ES) identified a novel homozygous mutation c.191delC (p.Ala64Valfs*33) in <jats:italic>MYF5<\/jats:italic> in the proband, with the father being heterozygous and the mother wild-type, as verified by Sanger sequencing. UPD identified from trio-ES variant call format data suggested the possibility of paternal UPD of chromosome 12 (UPD12pat) in the proband, further confirmed to be a complete isodisomy type of UPD by genome-wide single nucleotide polymorphism array. MYF5 was significantly downregulated by 69.14% (**<jats:italic>p<\/jats:italic> &amp;lt; 0.01) in HeLa cells transfected with mutant <jats:italic>MYF5<\/jats:italic> containing c.191delC compared to those transfected with the wild-type <jats:italic>MYF5<\/jats:italic>, resulting in a truncated protein with a size of \u223c20\u00a0kDa. In conclusion, this study identified a novel homozygous mutation in <jats:italic>MYF5<\/jats:italic>, broadening the genetic spectrum of EORVA and further deepening the understanding of this rare disease.<\/jats:p>","DOI":"10.3389\/fgene.2021.780363","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T10:33:01Z","timestamp":1643884381000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case Report: A Novel Homozygous Mutation in MYF5 Due to Paternal Uniparental Isodisomy of Chromosome 12 in a Case of External Ophthalmoplegia With Rib and Vertebral Anomalies"],"prefix":"10.3389","volume":"12","author":[{"given":"Qianqian","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenguang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Shang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranran","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangdong","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1002\/pd.5837","article-title":"Uniparental Disomy: Origin, Frequency, and Clinical Significance","volume":"41","author":"Benn","year":"2021","journal-title":"Prenatal Diagn."},{"key":"B2","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1136\/jmedgenet-2011-100372","article-title":"Pathogenic Aberrations Revealed Exclusively by Single Nucleotide Polymorphism (SNP) Genotyping Data in 5000 Samples Tested by Molecular Karyotyping","volume":"48","author":"Bruno","year":"2011","journal-title":"J. Med. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"743833","DOI":"10.3389\/fgene.2021.743833","article-title":"Case Report: A Case of Epileptic Disorder Associated with a Novel CNTN2 Frameshift Variant in Homozygosity Due to Maternal Uniparental Disomy","volume":"12","author":"Chen","year":"2021","journal-title":"Front. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.cca.2013.08.013","article-title":"Microarray Analysis Unmasked Paternal Uniparental Disomy of Chromosome 12 in a Patient with Isolated Sulfite Oxidase Deficiency","volume":"426","author":"Cho","year":"2013","journal-title":"Clinica Chim. Acta"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2410","DOI":"10.1111\/jth.13517","article-title":"Uniparental Disomy Causes Deficiencies of Vitamin K-dependent Proteins","volume":"14","author":"Dasi","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1038\/s41436-020-0782-9","article-title":"Diagnostic Testing for Uniparental Disomy: a Points to Consider Statement from the American College of Medical Genetics and Genomics (ACMG)","volume":"22","author":"Del Gaudio","year":"2020","journal-title":"Genet. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.ajhg.2018.05.003","article-title":"Recessive MYF5 Mutations Cause External Ophthalmoplegia, Rib, and Vertebral Anomalies","volume":"103","author":"Di Gioia","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1002\/ajmg.1320060207","article-title":"A New Genetic Concept: Uniparental Disomy and its Potential Effect, Isodisomy","volume":"6","author":"Engel","year":"1980","journal-title":"Am. J. Med. Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/s10038-021-00937-7","article-title":"A Patient with Silver-Russell Syndrome with Multilocus Imprinting Disturbance, and Schimke Immuno-Osseous Dysplasia Unmasked by Uniparental Isodisomy of Chromosome 2","volume":"66","author":"Hara-Isono","year":"2021","journal-title":"J. Hum. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.1002\/ajmg.a.32381","article-title":"Donnai-Barrow Syndrome (DBS\/FOAR) in a Child with a homozygousLRP2mutation Due to Complete Chromosome 2 Paternal Isodisomy","author":"Kantarci","year":"2008","journal-title":"Am. J. Med. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1101\/gr.160465.113","article-title":"A Novel Method for Detecting Uniparental Disomy from Trio Genotypes Identifies a Significant Excess in Children with Developmental Disorders","volume":"24","author":"King","year":"2014","journal-title":"Genome Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"707411","DOI":"10.3389\/fgene.2021.707411","article-title":"Identification of a Rare Case with Nagashima-type Palmoplantar Keratoderma and 18q Deletion Syndrome via Exome Sequencing and Low-Coverage Whole-Genome Sequencing","volume":"12","author":"Li","year":"2021","journal-title":"Front. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1002\/ajmg.b.30250","article-title":"Complete Maternal Uniparental Isodisomy of Chromosome 4 in a Subject with Major Depressive Disorder Detected by High Density SNP Genotyping Arrays","author":"Middleton","year":"2006","journal-title":"Am. J. Med. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1016\/j.ajhg.2019.09.016","article-title":"Characterization of Prevalence and Health Consequences of Uniparental Disomy in Four Million Individuals from the General Population","volume":"105","author":"Nakka","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"10456","DOI":"10.1073\/pnas.1202249109","article-title":"CD45-deficient Severe Combined Immunodeficiency Caused by Uniparental Disomy","volume":"109","author":"Roberts","year":"2012","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1111\/j.1399-0004.2010.01599.x","article-title":"Maternal Uniparental Isodisomy and Heterodisomy on Chromosome 6 Encompassing a CUL7 Gene Mutation Causing 3M Syndrome","volume":"80","author":"Sasaki","year":"2011","journal-title":"Clin. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1038\/ejhg.2014.63","article-title":"Genome-wide UPD Screening in Patients with Intellectual Disability","volume":"22","author":"Schroeder","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/s41436-020-01092-8","article-title":"Uniparental Disomy in a Population of 32,067 Clinical Exome Trios","volume":"23","author":"Scuffins","year":"2021","journal-title":"Genet. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1212\/wnl.0000000000002843","article-title":"Uniparental Disomy of Chromosome 16 Unmasks Recessive Mutations of FA2H\/SPG35 in 4 Families","volume":"87","author":"SoehnSoehn","year":"2016","journal-title":"Neurology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/s0002-9394(99)00467-5","article-title":"Evidence of Genetic Heterogeneity in Autosomal Recessive Congenital Fibrosis of the Extraocular Muscles","volume":"129","author":"Traboulsi","year":"2000","journal-title":"Am. J. Ophthalmol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/379823a0","article-title":"Functional Redundancy of the Muscle-specific Transcription Factors Myf5 and Myogenin","volume":"379","author":"Wang","year":"1996","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s00439-006-0314-y","article-title":"Achromatopsia: the CNGB3 p.T383fsX Mutation Results from a Founder Effect and Is Responsible for the Visual Phenotype in the Original Report of Uniparental Disomy 14","volume":"121","author":"Wiszniewski","year":"2007","journal-title":"Hum. Genet."},{"key":"B23","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1038\/s41436-019-0704-x","article-title":"Accurate Detection of Clinically Relevant Uniparental Disomy from Exome Sequencing Data","volume":"22","author":"Yauy","year":"2020","journal-title":"Genet. Med."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.780363\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T10:33:06Z","timestamp":1643884386000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.780363\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,3]]},"references-count":23,"alternative-id":["10.3389\/fgene.2021.780363"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2021.780363","relation":{},"ISSN":["1664-8021"],"issn-type":[{"type":"electronic","value":"1664-8021"}],"subject":[],"published":{"date-parts":[[2022,2,3]]},"article-number":"780363"}}