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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：玻璃综合征，源自染色体2q33.1微缺失，表现为智力残疾，小头畸形,癫痫,和鲜明的特点，包括小颌畸形,向下倾斜的睑裂,腭裂,拥挤的牙齿。最近,SATB2位于删除区域内，被鉴定为玻璃综合征的致病基因。已经报道了SATB2编码区内的许多致病变体。
目的：鉴于1号和2号染色体间从头相互易位的患者出现智力障碍和多种先天性异常，怀疑致病基因的破坏。这项研究试图确定患者的致病基因。
方法：进行长读全基因组测序，并分析候选基因的表达水平。
结果：断点检测成功。虽然染色体1上的断点破坏了RNF220,但它不被认为是遗传原因。相反，SATB2位于2号染色体上断裂点的约100kb端粒区。患者的临床特征与先前报道的玻璃综合征相似，尽管缺乏证实的SATB2表达减少。
结论：由于临床特征相似，患者被诊断为玻璃综合征。这使我们假设SATB2下游区域的破坏可能导致Glass综合征。在断点连接中鉴定的微同源性表明涉及微同源性介导的断裂诱导的修复机制或模板转换的潜在分子机制。
目的：鉴于1号和2号染色体间从头相互易位的患者出现智力障碍和多种先天性异常，怀疑致病基因的破坏。这项研究试图确定患者的致病基因。
方法：进行长读全基因组测序，并分析候选基因的表达水平。
结果：断点检测成功。虽然染色体1上的断点破坏了RNF220,但它不被认为是遗传原因。相反，SATB2位于2号染色体上断裂点的约100kb端粒区。患者的临床特征与先前报道的玻璃综合征相似，尽管缺乏证实的SATB2表达减少。
结论：由于临床特征相似，患者被诊断为玻璃综合征。这使我们假设SATB2下游区域的破坏可能导致Glass综合征。在断点连接中鉴定的微同源性表明涉及微同源性介导的断裂诱导的修复机制或模板转换的潜在分子机制。
