Glass syndrome derived from chromosomal breakage downstream region of SATB2

IF 1.4 4区 医学 Q4 CLINICAL NEUROLOGY
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引用次数: 0

Abstract

Background

Glass syndrome, derived from chromosomal 2q33.1 microdeletions, manifests with intellectual disability, microcephaly, epilepsy, and distinctive features, including micrognathia, down-slanting palpebral fissures, cleft palate, and crowded teeth. Recently, SATB2 located within the deletion region, was identified as the causative gene responsible for Glass syndrome. Numerous disease-causing variants within the SATB2 coding region have been reported.

Objective

Given the presentation of intellectual disability and multiple congenital anomalies in a patient with a de novo reciprocal translocation between chromosomes 1 and 2, disruption of the causative gene(s) was suspected. This study sought to identify the causative gene in the patient.

Methods

Long-read whole-genome sequencing was performed, and the expression level of the candidate gene was analyzed.

Results

The detection of breakpoints was successful. While the breakpoint on chromosome 1 disrupted RNF220, it was not deemed to be a genetic cause. Conversely, SATB2 is located in the approximately 100-kb telomeric region of the breakpoint on chromosome 2. The patient’s clinical features resembled those of previously reported cases of Glass syndrome, despite the lack of confirmed reduced SATB2 expression.

Conclusion

The patient was diagnosed with Glass syndrome due to the similarity in clinical features. This led us to hypothesize that disruption in the downstream region of SATB2 could result in Glass syndrome. The microhomologies identified in the breakpoint junctions indicate a potential molecular mechanism involving microhomology-mediated break-induced repair mechanism or template switching.

格拉斯综合征源于 SATB2 下游区域的染色体断裂。
背景:格拉斯综合征源于染色体 2q33.1 微缺失,表现为智力障碍、小头畸形、癫痫和独特的特征,包括小颌畸形、下斜睑裂、腭裂和牙齿拥挤。最近,位于缺失区的 SATB2 被确定为导致格拉斯综合征的致病基因。据报道,SATB2 编码区内存在大量致病变异:鉴于一名在 1 号染色体和 2 号染色体之间存在新发互易位点的患者表现出智力障碍和多种先天性畸形,因此怀疑致病基因发生了破坏。本研究试图确定该患者的致病基因:方法:进行长线程全基因组测序,分析候选基因的表达水平:结果:断点检测成功。虽然 1 号染色体上的断点破坏了 RNF220,但并未被认为是遗传原因。相反,SATB2位于2号染色体断点的约100kb端粒区。尽管没有证实 SATB2 表达减少,但患者的临床特征与之前报道的格拉斯综合征病例相似:结论:由于临床特征相似,该患者被诊断为格拉斯综合征。结论:由于临床特征相似,该患者被诊断为格拉斯综合征,这使我们推测 SATB2 下游区域的破坏可能导致格拉斯综合征。在断点连接处发现的微组构表明,潜在的分子机制涉及微组构介导的断裂诱导修复机制或模板转换。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Brain & Development
Brain & Development 医学-临床神经学
CiteScore
3.60
自引率
0.00%
发文量
153
审稿时长
50 days
期刊介绍: Brain and Development (ISSN 0387-7604) is the Official Journal of the Japanese Society of Child Neurology, and is aimed to promote clinical child neurology and developmental neuroscience. The journal is devoted to publishing Review Articles, Full Length Original Papers, Case Reports and Letters to the Editor in the field of Child Neurology and related sciences. Proceedings of meetings, and professional announcements will be published at the Editor''s discretion. Letters concerning articles published in Brain and Development and other relevant issues are also welcome.
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