Okur-Chung神经发育综合征:表型和基因型扩展的意义。

IF 1.5 4区 医学 Q4 GENETICS & HEREDITY
Haitian Nan, Min Chu, Jing Zhang, Deming Jiang, Yihao Wang, Liyong Wu
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引用次数: 0

摘要

背景:Okur-Chung神经发育综合征(OCNDS)是一种罕见的常染色体显性遗传疾病,由CSNK2A1的致病变异引起。该病以智力障碍、发育迟缓和多系统异常为特征:我们为一个中国家庭中的一名患者进行了全外显子组测序。方法:我们为一个中国家庭中的一名患者进行了全外显子组测序,并利用桑格测序法在家庭成员中进行了共分离研究。我们还使用该患者和野生型对照组的血液样本总 RNA 进行了逆转录和实时定量聚合酶链反应。通过全面检索PubMed数据库,对携带CSNK2A1致病变体的OCNDS患者进行了综述:我们在一个中国家庭中发现了一个新型 CSNK2A1 框移变异 p.Tyr323Leufs*16。31岁的女性患者饮食习惯异常、癫痫反复发作、语言障碍和智力障碍。她的母亲表现为产后疝气、脾肿大和易感染,但没有明显的发育障碍或智力障碍。遗传学研究发现,该患者及其母亲的 CSNK2A1 中都存在这种变异。转录分析表明,该变异可能导致无义介导的mRNA衰变,这表明单倍体缺乏是一种潜在的疾病机制。我们回顾了之前报道的 47 例 OCNDS 病例,发现携带 CSNK2A1 空变异的个体可能会表现出与语言障碍、面部特征畸形或智力障碍相关的症状,因此与携带错义变异的个体相比,其总体表型较轻:我们报告了一个新的框架移位变体 p.Tyr323Leufs*16,该变体出现在一个表型普遍较轻的 OCNDS 家族中。这项研究可能会拓宽与 OCNDS 相关的临床表现范围,并有助于深入了解这种疾病的基因型-表型相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Okur-Chung neurodevelopmental syndrome: Implications for phenotype and genotype expansion.

Okur-Chung neurodevelopmental syndrome: Implications for phenotype and genotype expansion.

Background: Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual disability, developmental delay, and multisystemic abnormalities.

Methods: We performed the whole-exome sequencing for a patient in a Chinese family. The co-segregation study using the Sanger sequencing method was performed among family members. Reverse transcription and quantitative real-time polymerase chain reaction were carried out using total RNA from blood samples of the proband and wild-type control subjects. A review of patients with OCNDS harboring CSNK2A1 pathogenic variants was conducted through a comprehensive search of the PubMed database.

Results: We identified a novel CSNK2A1 frameshift variant p.Tyr323Leufs*16 in a Chinese family. The proband, a 31-year-old female, presented with abnormal eating habits, recurrent seizures, language impairment, and intellectual disability. Her mother exhibited postnatal hernias, splenomegaly, and a predisposition to infections, but showed no significant developmental impairments or intellectual disability. Genetic studies revealed the presence of this variant in CSNK2A1 in both the proband and her mother. Transcription analysis revealed this variant may lead to nonsense-mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism. We reviewed 47 previously reported OCNDS cases and discovered that individuals carrying CSNK2A1 null variants may exhibit a diminished frequency of symptoms linked to language deficits, dysmorphic facial features, or intellectual disability, consequently presenting an overall milder phenotype when compared to those with missense variants.

Conclusion: We report a novel frameshift variant, p.Tyr323Leufs*16, in an OCNDS family with a generally mild phenotype. This study may broaden the spectrum of clinical presentations associated with OCNDS and contribute novel insights into the genotype-phenotype correlation of this condition.

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来源期刊
Molecular Genetics & Genomic Medicine
Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.20
自引率
0.00%
发文量
241
审稿时长
14 weeks
期刊介绍: Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.
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