AUTHOR=Li Qianqian , Zhu Xiaofan , Yu Chenguang , Shang Lin , Li Ranran , Wang Xia , Yang Yaping , Meng Jingjing , Kong Xiangdong 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 JOURNAL=Frontiers in Genetics VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.780363 DOI=10.3389/fgene.2021.780363 ISSN=1664-8021 ABSTRACT=

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 (MYF5) 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 MYF5 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% (**p < 0.01) in HeLa cells transfected with mutant MYF5 containing c.191delC compared to those transfected with the wild-type MYF5, resulting in a truncated protein with a size of ∼20 kDa. In conclusion, this study identified a novel homozygous mutation in MYF5, broadening the genetic spectrum of EORVA and further deepening the understanding of this rare disease.