An eight-case 1q21 region series: novel aberrations and clinical variability with new features
An eight-case 1q21 region series: novel aberrations and clinical variability with new features
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DOI：
10.1111/jir.12592
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发表时间：
2019-06-01
影响因子：
3.6
通讯作者：
Alikasifoglu, M.
中科院分区：
文献类型：
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作者：
Ceylan, A. C.;Sahin, I;Alikasifoglu, M.
背景1染色体1q21区域重排表现为多种表型，包括小头畸形、智力残疾、面部畸形、眼畸形、心脏缺陷、泌尿生殖系统异常、自闭症谱系障碍、精神疾病和癫痫。在这里，我们描述了8名患有1q21缺失和重复综合征的患者，以及新的缺失和发现。方法采用染色体微阵列技术检测基因拷贝数变异的存在。用对照和1号染色体1q21区的特异性引物进行定量聚合酶链式反应，对病例5进行RBM8A外显子1-6的基因组直接测序。结果拷贝数变异分析在8例患者中发现了7个1q21区域的缺失和1个重复。此外，有四个变异是新发现的，其中两个缺失是首次报道。其中1例(例7)表现为中度智能障碍和面部畸形，而染色体微阵列分析显示例7在1q21近端区域(GPR89A、PDZK1、CD160、POLR3C和NBPF12)有889kb的缺失。结论例5的缺失既不包括无血小板减少的桡骨综合征临界区，也不包括RBM8A基因，但有胸肌发育不良、尺骨和肱骨发育不良以及肋骨短弯曲，提示存在潜在的无血小板减少的桡骨区域修饰者。病例7的发现提示，1q21微缺失综合征区域的近端可能对临床表现的发生非常重要。在报告的病例中观察到一些新的发现，如桡骨和肱骨发育不良和脑干发育不良。目前的发现扩大了1q21异常的范围，并为该区域的基因-表型相关性提供了证据。
Background Rearrangement of the 1q21 region of chromosome 1 manifests as multiple phenotypes, including microcephaly, intellectual disability, dysmorphic facial features, eye abnormalities, cardiac defects, genitourinary anomalies, autism spectrum disorder, psychiatric conditions and seizures. Herein, we describe eight patients with 1q21 deletion and duplication syndromes, and novel deletions and findings. Methods Chromosomal microarray analysis was performed to identify the existence of copy number variation. Quantitative polymerase chain reaction was applied using specific primers for the control and 1q21 region of chromosome 1. Mutational analysis was performed in case 5 using direct genomic sequencing for exons 1-6 in RBM8A. Results Copy number variation analysis identified seven deletions and one duplication of the 1q21 region in the eight patients. In addition, four variations were de novo, and two deletions are reported here for the first time. One of the cases (case 7) presents moderate intellectual disability and dysmorphic facial findings, whereas chromosomal microarray analysis showed that case 7 had an 889-kb deletion in the 1q21 proximal region (GPR89A, PDZK1, CD160, POLR3C and NBPF12). Conclusion Although the deletion in case 5 did not include the thrombocytopenia-absent radius syndrome critical region or the RBM8A gene, he had pectoral muscle hypoplasia, radius and humerus hypoplasia and short curved ribs, which are indicative of a potential thrombocytopenia-absent radius region modifier. The findings in case 7 suggest that the proximal part of the 1q21 microdeletion syndrome region might be very important for the onset of clinical manifestations. Some novel findings were observed in the presented cases, such as radius and humerus hypoplasia and brain stem hypoplasia. The presented findings expand the spectrum of 1q21 aberrations and provide evidence of genotype-phenotype correlations for this region.