Exome Sequencing Reveals De Novo Variants in Congenital Scoliosis.

IF 0.4 Q4 PEDIATRICS

Journal of pediatric genetics Pub Date : 2021-04-14 eCollection Date: 2022-12-01 DOI:10.1055/s-0041-1726282

Kohei Murakami, Shingo Kikugawa, Shoji Seki, Hidetomi Terai, Takako Suzuki, Masaki Nakano, Jun Takahashi, Yukio Nakamura

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引用次数: 0

Abstract

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.

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外显子组测序揭示先天性脊柱侧凸的从头变异。

先天性脊柱侧弯(CS)是一种脊柱侧弯，其特征是存在椎体异常。TBX6基因的致病性遗传变异是导致CS的原因之一。然而，由于许多临床诊断的CS病例没有已知的TBX6基因变异，本研究旨在通过外显子组测序(ES)发现与CS疾病易感性相关的新基因。本研究采用ES对5名日本CS患者及其健康父母或姐妹进行队列研究，共5个家庭16个样本。使用SIFT、polyphen2、Mutation Taster和CADD进行变异解释。通过ES鉴定并通过Sanger测序确认了4个新变体:1个移码变体(SHISA3)和3个错义变体(AGBL5、HDAC4和PDE2A)。ES还在MOCOS基因中发现了1个纯合变异。所有这些变异通过SIFT、polyphen2、Mutation Taster和/或CADD预测为有害的。在这项研究中发现的新生变异的数量完全是偶然预期的。需要额外的功能研究或使用Gene Matcher收集匹配的患者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Journal of pediatric genetics PEDIATRICS-

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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.