• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

导致X连锁智力障碍的基因中的新变异

Novel Variations in the Gene Causing X-Linked Intellectual Disability.

作者信息

Wu Po-Ming, Yu Wen-Hao, Chiang Chi-Wu, Wu Chen-Yu, Chen Jia-Shing, Tu Yi-Fang

机构信息

Department of Pediatrics (P.-M.W., W.-H.Y., C.-Y.W., Y.-F.T.), National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan; School of Medicine for International Students (J.-S.C.), I-Shou University, Kaohsiung; Institute of Clinical Medicine (W.-H.Y., Y.-F.T.), College of Medicine, National Cheng Kung University, Tainan; Institute of Molecular Medicine (C.-W.C.), College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

Neurol Genet. 2021 Dec 3;8(1):e646. doi: 10.1212/NXG.0000000000000646. eCollection 2022 Feb.

DOI:10.1212/NXG.0000000000000646
PMID:34877407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8641966/
Abstract

BACKGROUND AND OBJECTIVES

To investigate the pathogenicity of 2 novel variations, report the clinical and neuroimaging findings, and review the available literature.

METHODS

Physical examinations, structural neuroimaging studies, and exome sequence analysis were performed. KDM5C constructs were used to study the effect of the variations in transfected cells.

RESULTS

We identified 2 novel variations c.2233C>G and c.3392_3393delAG in the gene harboring from 2 Chinese families with X-linked intellectual disability (ID). The affected male patients exhibited severe ID, short stature, and facial dysmorphism. The 1 with c.3392_3393delAG additionally had epilepsy and autistic spectrum disorder (ASD). Transiently transfected mutant KDM5C constructs both reduced protein expression and stability and decreased histone demethylase activities in cells. Reviewing the available literature, we found that the associated ASD tended to occur in patients with variations near the C-terminus of KDM5C.

DISCUSSION

We report the clinical, molecular genetic, and pathologic features in patients with novel variations of . The variability of the clinical phenotype in addition to an ID may associate with altered particular parts of KDM5C.

摘要

背景与目的

研究2种新变异的致病性，报告临床和神经影像学发现，并回顾现有文献。

方法

进行体格检查、结构神经影像学研究和外显子序列分析。使用KDM5C构建体研究转染细胞中变异的影响。

结果

我们在来自2个患有X连锁智力残疾（ID）的中国家庭的基因中鉴定出2种新变异c.2233C>G和c.3392_3393delAG。受影响的男性患者表现出严重的ID、身材矮小和面部畸形。携带c.3392_3393delAG变异的患者还患有癫痫和自闭症谱系障碍（ASD）。瞬时转染的突变KDM5C构建体均降低了细胞中的蛋白质表达和稳定性，并降低了组蛋白去甲基化酶活性。回顾现有文献，我们发现相关的ASD倾向于发生在KDM5C C末端附近有变异的患者中。

讨论

我们报告了具有新变异患者的临床、分子遗传学和病理学特征。除ID外，临床表型的变异性可能与KDM5C特定部位的改变有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cf/8641966/c5531b8ad225/NG2021017055f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cf/8641966/cf2f67177749/NG2021017055f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cf/8641966/eddd0789bd93/NG2021017055f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cf/8641966/fdc4b28925c3/NG2021017055f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cf/8641966/2b4628645825/NG2021017055f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cf/8641966/c5531b8ad225/NG2021017055f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cf/8641966/cf2f67177749/NG2021017055f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cf/8641966/eddd0789bd93/NG2021017055f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cf/8641966/fdc4b28925c3/NG2021017055f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cf/8641966/2b4628645825/NG2021017055f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2cf/8641966/c5531b8ad225/NG2021017055f5.jpg

相似文献

1
Novel Variations in the Gene Causing X-Linked Intellectual Disability.导致X连锁智力障碍的基因中的新变异
Neurol Genet. 2021 Dec 3;8(1):e646. doi: 10.1212/NXG.0000000000000646. eCollection 2022 Feb.
2
Further delineation of the female phenotype with KDM5C disease causing variants: 19 new individuals and review of the literature.进一步描述 KDM5C 致病变异导致的女性表型：19 例新病例及文献复习。
Clin Genet. 2020 Jul;98(1):43-55. doi: 10.1111/cge.13755. Epub 2020 May 29.
3
KDM5C mutational screening among males with intellectual disability suggestive of X-Linked inheritance and review of the literature.对提示X连锁遗传的智力障碍男性进行KDM5C突变筛查及文献综述。
Eur J Med Genet. 2014 Mar;57(4):138-44. doi: 10.1016/j.ejmg.2014.02.011. Epub 2014 Feb 27.
4
Altered Gene-Regulatory Function of KDM5C by a Novel Mutation Associated With Autism and Intellectual Disability.与自闭症和智力残疾相关的新型突变导致KDM5C基因调控功能改变。
Front Mol Neurosci. 2018 Apr 4;11:104. doi: 10.3389/fnmol.2018.00104. eCollection 2018.
5
Sexually Dimorphic Alterations in the Transcriptome and Behavior with Loss of Histone Demethylase .性别二态性改变的转录组和行为与组蛋白去甲基化酶的缺失。
Cells. 2023 Feb 16;12(4):637. doi: 10.3390/cells12040637.
6
Microdeletion of the escape genes KDM5C and IQSEC2 in a girl with severe intellectual disability and autistic features.一名患有严重智力障碍和自闭症特征女孩中逃逸基因KDM5C和IQSEC2的微缺失。
Eur J Med Genet. 2015 May;58(5):324-7. doi: 10.1016/j.ejmg.2015.03.003. Epub 2015 Apr 7.
7
A female case with novel KDM5C heterozygous variation presenting with Claes-Jensen type-like phonotype.一名女性病例存在新型 KDM5C 杂合变异，表现出类 Claes-Jensen 型表型。
BMC Neurol. 2022 Dec 19;22(1):491. doi: 10.1186/s12883-022-03023-3.
8
Caregiver-reported characteristics of children diagnosed with pathogenic variants in KDM5C.照顾者报告的 KDM5C 致病性变异患儿特征。
Am J Med Genet A. 2021 Oct;185(10):2951-2958. doi: 10.1002/ajmg.a.62381. Epub 2021 Jun 4.
9
A regulatory path associated with X-linked intellectual disability and epilepsy links KDM5C to the polyalanine expansions in ARX.一种与 X 连锁智力残疾和癫痫相关的调节途径将 KDM5C 与 ARX 中的多聚丙氨酸扩展联系起来。
Am J Hum Genet. 2013 Jan 10;92(1):114-25. doi: 10.1016/j.ajhg.2012.11.008. Epub 2012 Dec 13.
10
Molecular and cellular events linking variants in the histone demethylase KDM5C to the intellectual disability disorder Claes-Jensen syndrome.将组蛋白去甲基化酶 KDM5C 中的变异与智力残疾障碍 Claes-Jensen 综合征相关的分子和细胞事件。
FEBS J. 2022 Dec;289(24):7776-7787. doi: 10.1111/febs.16204. Epub 2021 Sep 29.

引用本文的文献

1
First reported case of de Novo claes-jensen syndrome (CJS) in Palestine: diagnostic challenges and genetic insights.巴勒斯坦首例新发克莱斯-詹森综合征（CJS）病例：诊断挑战与遗传学见解
BMC Pediatr. 2025 May 9;25(1):368. doi: 10.1186/s12887-025-05709-2.
2
A novel KDM5C mutation associated with intellectual disability: molecular mechanisms and clinical implications.一种与智力残疾相关的新型KDM5C突变：分子机制及临床意义
Ital J Pediatr. 2025 Feb 14;51(1):47. doi: 10.1186/s13052-025-01887-y.
3
Traversing the epigenetic landscape: DNA methylation from retina to brain in development and disease.

本文引用的文献

1
Comorbidities associated with genetic abnormalities in children with intellectual disability.智力残疾儿童的遗传异常相关合并症。
Sci Rep. 2021 Mar 22;11(1):6563. doi: 10.1038/s41598-021-86131-3.
2
X-linked mental retardation and severe short stature with a novel mutation of the gene.X连锁智力迟钝伴严重身材矮小及该基因的一种新突变
Clin Pediatr Endocrinol. 2021;30(1):61-64. doi: 10.1297/cpe.30.61. Epub 2021 Jan 5.
3
[Clinical features and gene variant of a pedigree affected with X-linked recessive mental retardation Claes-Jensen type].
穿越表观遗传景观：发育和疾病过程中从视网膜到大脑的DNA甲基化
Front Cell Neurosci. 2024 Nov 29;18:1499719. doi: 10.3389/fncel.2024.1499719. eCollection 2024.
4
Sex chromosome-encoded protein homologs: current progress and open questions.性染色体编码蛋白同源物：当前的进展和未解决的问题。
Nat Struct Mol Biol. 2024 Aug;31(8):1156-1166. doi: 10.1038/s41594-024-01362-y. Epub 2024 Aug 9.
5
Expanding the Spectrum of Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype-Phenotype Correlations.拓展神经发育障碍谱：一位年轻女性新的散发型无义变异，及其潜在的基因型-表型相关性。
Genes (Basel). 2022 Dec 1;13(12):2266. doi: 10.3390/genes13122266.
6
A female case with novel KDM5C heterozygous variation presenting with Claes-Jensen type-like phonotype.一名女性病例存在新型 KDM5C 杂合变异，表现出类 Claes-Jensen 型表型。
BMC Neurol. 2022 Dec 19;22(1):491. doi: 10.1186/s12883-022-03023-3.
7
Expanding the genetics and phenotypic spectrum of Lysine-specific demethylase 5C (KDM5C): a report of 13 novel variants.扩展赖氨酸特异性去甲基酶 5C（KDM5C）的遗传学和表型谱：13 个新变异体的报告。
Eur J Hum Genet. 2023 Feb;31(2):202-215. doi: 10.1038/s41431-022-01233-4. Epub 2022 Nov 25.
8
Genetics and Epigenetics of the X and Y Chromosomes in the Sexual Differentiation of the Brain.X 和 Y 染色体在大脑性别分化中的遗传学和表观遗传学。
Int J Mol Sci. 2022 Oct 14;23(20):12288. doi: 10.3390/ijms232012288.
[X连锁隐性克拉斯-延森型智力障碍家系的临床特征与基因变异]
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2020 Dec 10;37(12):1352-1355. doi: 10.3760/cma.j.cn511374-20191218-00643.
4
Development of a multiplex qPCR-based approach for the diagnosis of Dirofilaria immitis, D. repens and Acanthocheilonema reconditum.建立一种基于多重 qPCR 的方法，用于诊断犬恶丝虫、猫恶丝虫和旋尾线虫。
Parasit Vectors. 2020 Jun 22;13(1):319. doi: 10.1186/s13071-020-04185-0.
5
Further delineation of the female phenotype with KDM5C disease causing variants: 19 new individuals and review of the literature.进一步描述 KDM5C 致病变异导致的女性表型：19 例新病例及文献复习。
Clin Genet. 2020 Jul;98(1):43-55. doi: 10.1111/cge.13755. Epub 2020 May 29.
6
DNA methylation fingerprint of monozygotic twins and their singleton sibling with intellectual disability carrying a novel KDM5C mutation.携带新型KDM5C突变的智障单卵双胞胎及其单胎同胞的DNA甲基化指纹图谱。
Eur J Med Genet. 2020 Mar;63(3):103737. doi: 10.1016/j.ejmg.2019.103737. Epub 2019 Aug 13.
7
Histone H3 lysine K4 methylation and its role in learning and memory.组蛋白 H3 赖氨酸 K4 甲基化及其在学习和记忆中的作用。
Epigenetics Chromatin. 2019 Jan 7;12(1):7. doi: 10.1186/s13072-018-0251-8.
8
Altered Gene-Regulatory Function of KDM5C by a Novel Mutation Associated With Autism and Intellectual Disability.与自闭症和智力残疾相关的新型突变导致KDM5C基因调控功能改变。
Front Mol Neurosci. 2018 Apr 4;11:104. doi: 10.3389/fnmol.2018.00104. eCollection 2018.
9
Loss of Kdm5c Causes Spurious Transcription and Prevents the Fine-Tuning of Activity-Regulated Enhancers in Neurons.Kdm5c 的缺失会导致虚假转录，并阻止神经元中活性调节增强子的精细调控。
Cell Rep. 2017 Oct 3;21(1):47-59. doi: 10.1016/j.celrep.2017.09.014.
10
Different X-linked KDM5C mutations in affected male siblings: is maternal reversion error involved?患病男性同胞中不同的X连锁KDM5C突变：是否涉及母源回复突变错误？
Clin Genet. 2016 Sep;90(3):276-81. doi: 10.1111/cge.12767. Epub 2016 Mar 23.