Large Chromosome 2p Duplication-Associated Mechanisms and Clinical Presentations.

IF 1.7 4区 生物学 Q4 CELL BIOLOGY
Cytogenetic and Genome Research Pub Date : 2023-01-01 Epub Date: 2023-07-27 DOI:10.1159/000533218
Xiaolan Fang, Benjamin Hilton, Katie Clarkson, R Curtis Rogers, Richard Schroer, Anna Childers, Wesley G Patterson, Jessica M Davis, David B Everman, Barbara R DuPont
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引用次数: 0

Abstract

Chromosome 2p (chr2p) duplication, also known as trisomy 2p, is a rare chromosome abnormality associated with developmental delay, intellectual disability, behavioral problems, and distinctive facial features. Most of the reported cases involving trisomy 2p include additional copy number variants (CNVs) in other regions of the genome and are usually small in size. Little is known about the clinical outcomes of large duplications of chr2p as the sole cytogenetic abnormality. In this study, 193 samples at the Greenwood Genetic Center (GGC) with CNVs involving chr2p were evaluated, out of which 86 had chr2p duplications. Among them, 8 patients were identified with large chr2p duplications ranging in size from 9.3 Mb to 89 Mb, and no deletions or duplications involving other chromosomes were identified in those patients. These duplications were associated with inverted duplication, tandem duplication, and duplication as the result of translocation, with no additional CNVs identified by microarray analysis. Confirmation by conventional cytogenetics was performed in 7 of the 8 patients, and the translocations were confirmed by fluorescence in situ hybridization. Interestingly, 1 patient was found to have mosaic complete trisomy 2p as the result of an unbalanced de novo (X;2) chromosomal translocation. X-inactivation was skewed toward the derivative X chromosome, yet it did not appear to extend into the chromosome 2 material. Various shared clinical manifestations were observed in the individuals in this study, including developmental delay, hemifacial hypoplasia, cleft palate, and short stature, and they also have distinct features such as hypotonia, cerebellar hypogenesis, and corpus callosum agenesis, which might result from a gene dosage effect of the duplication. In conclusion, single-event large chr2p duplications can result from different mechanisms, including inverted or tandem duplications within chromosome 2, or translocations involving chromosome 2 and other chromosomes. Partial or complete trisomy 2p is commonly associated with developmental delay, and additional clinical features may be related to gene dosage effects.

大染色体2p重复的相关机制和临床表现。
2p染色体(chr2p)重复,也称为2p三体,是一种罕见的染色体异常,与发育迟缓、智力残疾、行为问题和独特的面部特征有关。大多数报告的涉及2p三体的病例包括基因组其他区域的额外拷贝数变异(CNVs),并且通常很小。对于chr2p作为唯一的细胞遗传学异常的大量重复的临床结果知之甚少。本研究对格林伍德遗传中心(GGC)的193份涉及chr2p的CNVs样本进行了评估,其中86份存在chr2p重复。其中8例患者被鉴定出大的chr2p重复,大小从9.3 Mb到89 Mb不等,未发现其他染色体的缺失或重复。这些复制与倒置复制、串联复制和易位复制有关,微阵列分析没有发现额外的CNVs。8例患者中有7例经常规细胞遗传学证实,并通过荧光原位杂交证实易位。有趣的是,1例患者发现由于新生(X;2)染色体易位不平衡而患有马赛克完全2p三体。X染色体失活倾向于衍生的X染色体,但它似乎没有延伸到2号染色体材料。本研究中个体的共同临床表现有发育迟缓、半面发育不全、腭裂、身材矮小等,但也有张力低下、小脑发育不全、胼胝体发育不全等明显特征,可能是由于复制的基因剂量效应所致。综上所述,单事件大chr2p复制可以由不同的机制引起,包括2号染色体内的反向或串联复制,或2号染色体和其他染色体的易位。部分或完全2p三体通常与发育迟缓有关,其他临床特征可能与基因剂量效应有关。
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来源期刊
Cytogenetic and Genome Research
Cytogenetic and Genome Research 生物-细胞生物学
CiteScore
3.10
自引率
5.90%
发文量
25
审稿时长
1 months
期刊介绍: During the last decades, ''Cytogenetic and Genome Research'' has been the leading forum for original reports and reviews in human and animal cytogenetics, including molecular, clinical and comparative cytogenetics. In recent years, most of its papers have centered on genome research, including gene cloning and sequencing, gene mapping, gene regulation and expression, cancer genetics, comparative genetics, gene linkage and related areas. The journal also publishes key papers on chromosome aberrations in somatic, meiotic and malignant cells. Its scope has expanded to include studies on invertebrate and plant cytogenetics and genomics. Also featured are the vast majority of the reports of the International Workshops on Human Chromosome Mapping, the reports of international human and animal chromosome nomenclature committees, and proceedings of the American and European cytogenetic conferences and other events. In addition to regular issues, the journal has been publishing since 2002 a series of topical issues on a broad variety of themes from cytogenetic and genome research.
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