{"title":"外显子组测序揭示先天性脊柱侧凸的从头变异。","authors":"Kohei Murakami, Shingo Kikugawa, Shoji Seki, Hidetomi Terai, Takako Suzuki, Masaki Nakano, Jun Takahashi, Yukio Nakamura","doi":"10.1055/s-0041-1726282","DOIUrl":null,"url":null,"abstract":"<p><p>Congenital scoliosis (CS) is a lateral curvature of the spine characterized by the presence of vertebral anomalies. Pathogenic genetic variants in the <i>TBX6</i> gene are one of the causes of CS. However, since many clinically diagnosed cases of CS are without known <i>TBX6</i> gene variations, this study aims to uncover new genes related to disease susceptibility of CS by exome sequencing (ES). This study employed ES in a cohort of 5 Japanese patients with CS and their healthy parents or a sister for a total of 16 samples among 5 families. Variant interpretation was performed using SIFT, PolyPhen-2, Mutation Taster, and CADD. Four de novo variants were identified by ES and confirmed by Sanger sequencing: 1 frameshift variant ( <i>SHISA3</i> ) and 3 missense variants ( <i>AGBL5</i> , <i>HDAC4</i> , and <i>PDE2A</i> ). ES also uncovered 1 homozygous variant in the <i>MOCOS</i> gene. All of these variants were predicted to be deleterious by SIFT, PolyPhen-2, Mutation Taster, and/or CADD. The number of de novo variants identified in this study was exactly what would be expected by chance. Additional functional studies or gathering matched patients using Gene Matcher are needed.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"11 4","pages":"287-291"},"PeriodicalIF":0.4000,"publicationDate":"2021-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578779/pdf/10-1055-s-0041-1726282.pdf","citationCount":"0","resultStr":"{\"title\":\"Exome Sequencing Reveals De Novo Variants in Congenital Scoliosis.\",\"authors\":\"Kohei Murakami, Shingo Kikugawa, Shoji Seki, Hidetomi Terai, Takako Suzuki, Masaki Nakano, Jun Takahashi, Yukio Nakamura\",\"doi\":\"10.1055/s-0041-1726282\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Congenital scoliosis (CS) is a lateral curvature of the spine characterized by the presence of vertebral anomalies. Pathogenic genetic variants in the <i>TBX6</i> gene are one of the causes of CS. However, since many clinically diagnosed cases of CS are without known <i>TBX6</i> gene variations, this study aims to uncover new genes related to disease susceptibility of CS by exome sequencing (ES). This study employed ES in a cohort of 5 Japanese patients with CS and their healthy parents or a sister for a total of 16 samples among 5 families. Variant interpretation was performed using SIFT, PolyPhen-2, Mutation Taster, and CADD. Four de novo variants were identified by ES and confirmed by Sanger sequencing: 1 frameshift variant ( <i>SHISA3</i> ) and 3 missense variants ( <i>AGBL5</i> , <i>HDAC4</i> , and <i>PDE2A</i> ). ES also uncovered 1 homozygous variant in the <i>MOCOS</i> gene. All of these variants were predicted to be deleterious by SIFT, PolyPhen-2, Mutation Taster, and/or CADD. The number of de novo variants identified in this study was exactly what would be expected by chance. Additional functional studies or gathering matched patients using Gene Matcher are needed.</p>\",\"PeriodicalId\":16695,\"journal\":{\"name\":\"Journal of pediatric genetics\",\"volume\":\"11 4\",\"pages\":\"287-291\"},\"PeriodicalIF\":0.4000,\"publicationDate\":\"2021-04-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578779/pdf/10-1055-s-0041-1726282.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of pediatric genetics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1055/s-0041-1726282\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/12/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pediatric genetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1055/s-0041-1726282","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/12/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"PEDIATRICS","Score":null,"Total":0}
Exome Sequencing Reveals De Novo Variants in Congenital Scoliosis.
Congenital scoliosis (CS) is a lateral curvature of the spine characterized by the presence of vertebral anomalies. Pathogenic genetic variants in the TBX6 gene are one of the causes of CS. However, since many clinically diagnosed cases of CS are without known TBX6 gene variations, this study aims to uncover new genes related to disease susceptibility of CS by exome sequencing (ES). This study employed ES in a cohort of 5 Japanese patients with CS and their healthy parents or a sister for a total of 16 samples among 5 families. Variant interpretation was performed using SIFT, PolyPhen-2, Mutation Taster, and CADD. Four de novo variants were identified by ES and confirmed by Sanger sequencing: 1 frameshift variant ( SHISA3 ) and 3 missense variants ( AGBL5 , HDAC4 , and PDE2A ). ES also uncovered 1 homozygous variant in the MOCOS gene. All of these variants were predicted to be deleterious by SIFT, PolyPhen-2, Mutation Taster, and/or CADD. The number of de novo variants identified in this study was exactly what would be expected by chance. Additional functional studies or gathering matched patients using Gene Matcher are needed.
期刊介绍：
The Journal of Pediatric Genetics is an English multidisciplinary peer-reviewed international journal publishing articles on all aspects of genetics in childhood and of the genetics of experimental models. These topics include clinical genetics, molecular genetics, biochemical genetics, medical genetics, dysmorphology, teratology, genetic counselling, genetic engineering, formal genetics, neuropsychiatric genetics, behavioral genetics, community genetics, cytogenetics, hereditary or syndromic cancer genetics, genetic mapping, reproductive genetics, fetal pathology and prenatal diagnosis, multiple congenital anomaly syndromes, and molecular embryology of birth defects. Journal of Pediatric Genetics provides an in-depth update on new subjects and current comprehensive coverage of the latest techniques used in the diagnosis of childhood genetics. Journal of Pediatric Genetics encourages submissions from all authors throughout the world. The following articles will be considered for publication: editorials, original and review articles, short report, rapid communications, case reports, letters to the editor, and book reviews. The aim of the journal is to share and disseminate knowledge between all disciplines in the field of pediatric genetics. This journal is a publication of the World Pediatric Society: http://www.worldpediatricsociety.org/ The Journal of Pediatric Genetics is available in print and online. Articles published ahead of print are available via the eFirst service on the Thieme E-Journals platform.
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