在表观遗传学和染色质诊所的5年经验:我们学到了什么,我们将何去何从?

IF 3.8 2区 生物学 Q2 GENETICS & HEREDITY
Human Genetics Pub Date : 2024-04-01 Epub Date: 2023-03-23 DOI:10.1007/s00439-023-02537-1
Jacqueline R Harris, Christine W Gao, Jacquelyn F Britton, Carolyn D Applegate, Hans T Bjornsson, Jill A Fahrner
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引用次数: 0

摘要

约翰霍普金斯大学的多学科表观遗传学和染色质诊所为涉及表观遗传学紊乱的罕见疾病患者提供全面的医疗护理。最初以经典印记疾病为中心,焦点转移到由表观遗传机制基因的致病性种系变异引起的快速出现的遗传疾病组。这些统称为表观遗传机制的孟德尔障碍(mdem),或更广泛地称为色素病。在五年中,432名患者完成了741次门诊就诊,其中153人确诊了表观遗传学诊断。其中,115人患有26个mdem中的一个,每个人都表现出全面发育迟缓和/或智力残疾。这支持了先前的观察,即智力残疾是mdem最常见的表型特征。我们诊所的其他常见表型包括生长异常和神经发育问题,特别是张力不足、注意力缺陷/多动障碍(ADHD)和焦虑,癫痫和自闭症不太常见。总的来说,我们的患者群体代表了更广泛的mdem群体,包括大多数常染色体显性遗传病,对书写者的影响大于对染色质标记的擦除者、读取者和重塑者的影响。具有读取器和酶结构域的双功能组分的代表性增加。正如预期的那样,诊断主要是通过测序进行的,但在某些情况下,DNA甲基化分析也有助于诊断。我们的诊所帮助促进了两种新疾病的发现,我们的提供者正在积极开发和实施新的治疗策略。这些数据和我们超过60%的高随访率表明,我们正在实现我们的使命,即诊断、学习并为表观遗传学紊乱的患者提供最佳护理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Five years of experience in the Epigenetics and Chromatin Clinic: what have we learned and where do we go from here?

Five years of experience in the Epigenetics and Chromatin Clinic: what have we learned and where do we go from here?

Five years of experience in the Epigenetics and Chromatin Clinic: what have we learned and where do we go from here?

Five years of experience in the Epigenetics and Chromatin Clinic: what have we learned and where do we go from here?

The multidisciplinary Epigenetics and Chromatin Clinic at Johns Hopkins provides comprehensive medical care for individuals with rare disorders that involve disrupted epigenetics. Initially centered on classical imprinting disorders, the focus shifted to the rapidly emerging group of genetic disorders resulting from pathogenic germline variants in epigenetic machinery genes. These are collectively called the Mendelian disorders of the epigenetic machinery (MDEMs), or more broadly, Chromatinopathies. In five years, 741 clinic visits have been completed for 432 individual patients, with 153 having confirmed epigenetic diagnoses. Of these, 115 individuals have one of 26 MDEMs with every single one exhibiting global developmental delay and/or intellectual disability. This supports prior observations that intellectual disability is the most common phenotypic feature of MDEMs. Additional common phenotypes in our clinic include growth abnormalities and neurodevelopmental issues, particularly hypotonia, attention-deficit/hyperactivity disorder (ADHD), and anxiety, with seizures and autism being less common. Overall, our patient population is representative of the broader group of MDEMs and includes mostly autosomal dominant disorders impacting writers more so than erasers, readers, and remodelers of chromatin marks. There is an increased representation of dual function components with a reader and an enzymatic domain. As expected, diagnoses were made mostly by sequencing but were aided in some cases by DNA methylation profiling. Our clinic has helped to facilitate the discovery of two new disorders, and our providers are actively developing and implementing novel therapeutic strategies for MDEMs. These data and our high follow-up rate of over 60% suggest that we are achieving our mission to diagnose, learn from, and provide optimal care for our patients with disrupted epigenetics.

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来源期刊
Human Genetics
Human Genetics 生物-遗传学
CiteScore
10.80
自引率
3.80%
发文量
94
审稿时长
1 months
期刊介绍: Human Genetics is a monthly journal publishing original and timely articles on all aspects of human genetics. The Journal particularly welcomes articles in the areas of Behavioral genetics, Bioinformatics, Cancer genetics and genomics, Cytogenetics, Developmental genetics, Disease association studies, Dysmorphology, ELSI (ethical, legal and social issues), Evolutionary genetics, Gene expression, Gene structure and organization, Genetics of complex diseases and epistatic interactions, Genetic epidemiology, Genome biology, Genome structure and organization, Genotype-phenotype relationships, Human Genomics, Immunogenetics and genomics, Linkage analysis and genetic mapping, Methods in Statistical Genetics, Molecular diagnostics, Mutation detection and analysis, Neurogenetics, Physical mapping and Population Genetics. Articles reporting animal models relevant to human biology or disease are also welcome. Preference will be given to those articles which address clinically relevant questions or which provide new insights into human biology. Unless reporting entirely novel and unusual aspects of a topic, clinical case reports, cytogenetic case reports, papers on descriptive population genetics, articles dealing with the frequency of polymorphisms or additional mutations within genes in which numerous lesions have already been described, and papers that report meta-analyses of previously published datasets will normally not be accepted. The Journal typically will not consider for publication manuscripts that report merely the isolation, map position, structure, and tissue expression profile of a gene of unknown function unless the gene is of particular interest or is a candidate gene involved in a human trait or disorder.
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