[Clinical features and genetic analysis of a child with Congenital disorder of glycosylation due to novel variants of COG6 gene].

Liyu Zhang, Ying Yang, Fengyu Che, Benchang Li, Lidangzhi Mo, Guoxia Wang, Jiangang Zhao
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引用次数: 0

Abstract

Objective: To analyze the clinical characteristics of a child with Congenital disorder of glycosylation due to compound heterozygous variants of COG6 gene (COG6-CDG).

Methods: A child who was admitted to Xi'an Children's Hospital on January 10, 2023 was selected as the study subject. Clinical data were collected. Pathogenic variants were analyzed by whole exome sequencing, and candidate variants were verified by Sanger sequencing, in vitro experiments and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Xi'an Children's Hospital (Ethics No. 20230101).

Results: The child, a 1-month-8-day-old male, was admitted for diarrhea and weight loss for one month. He had presented with cholestasis, diarrhea, facial dysmorphism, poor response, bilateral Simian crease, and brain atrophy. After discharge, he had continued to have high fever, feeding difficulty, and deceased finally. Whole exome sequencing results showed that he had harbored compound heterozygous variants of the COG6 gene, namely c.807delT (p.F269Lfs*37) and c.1746+1G>C (p.Gly565_Met582del). Sanger sequencing verified that the variants were inherited from his father and mother, respectively. In vitro experiments verified that the c.1746+1G>C variant could affect the mRNA splicing and produce a truncated protein, whilst the c.807delT variant could significantly reduce gene expression at both mRNA and protein levels. Based on the guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP), the variants were classified as pathogenic (PVS1+PM3+PM2_Supporting) and likely pathogenic (PVS1+PM2_Supporting), respectively.

Conclusion: The c.807delT (p.F269Lfs*37) and c.1746+1G>C (p.Gly565_Met582del) compound heterozygous variants of the COG6 gene probably underlay the pathogenesis of this child. Above finding has enriched the mutational spectrum of COG6-CDG and provided a basis for the genetic counseling for this family.

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[一名因 COG6 基因新型变体而患有先天性糖基化紊乱的儿童的临床特征和遗传分析]。
摘要分析COG6基因复合杂合子变异(COG6-CDG)所致先天性糖基化紊乱患儿的临床特征:方法:选取 2023 年 1 月 10 日在西安市儿童医院住院的一名患儿作为研究对象。收集临床数据。通过全外显子测序分析致病变异,通过桑格测序、体外实验和生物信息学分析验证候选变异。本研究获得了西安市儿童医院医学伦理委员会的批准(伦理编号:20230101):患儿为 1 个月至 8 天大的男性,因腹泻和体重减轻入院一个月。他曾出现胆汁淤积、腹泻、面部畸形、反应差、双侧西米氏皱襞和脑萎缩。出院后,他继续发高烧,进食困难,最后死亡。全外显子测序结果显示,他的COG6基因存在复合杂合变异,即c.807delT(p.F269Lfs*37)和c.1746+1G>C(p.Gly565_Met582del)。桑格测序验证了这些变体分别遗传自他的父亲和母亲。体外实验证实,c.1746+1G>C 变异可影响 mRNA 的剪接并产生截短蛋白,而 c.807delT 变异可显著降低基因在 mRNA 和蛋白水平的表达。根据美国医学遗传学与基因组学学院和分子病理学协会(ACMG-AMP)的指导方针,这些变异体分别被归类为致病性(PVS1+PM3+PM2_支持性)和可能致病性(PVS1+PM2_支持性):结论:COG6基因的c.807delT (p.F269Lfs*37)和c.1746+1G>C (p.Gly565_Met582del)复合杂合变异可能是该患儿发病机制的基础。上述发现丰富了COG6-CDG的突变谱,为该家族的遗传咨询提供了依据。
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来源期刊
中华医学遗传学杂志
中华医学遗传学杂志 Medicine-Medicine (all)
CiteScore
0.50
自引率
0.00%
发文量
9521
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.
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