Balanced chromosomal rearrangements are usually associated with a normal phenotype, although in some individuals, phenotypic alterations are observed. In these patients, molecular characterization of the breakpoints can reveal the pathogenic mechanism, providing the annotation of disease-associated loci and a better genotype-phenotype correlation. In this study, we describe a patient with a balanced reciprocal translocation between 4q27 and 7p22 associated with neurodevelopmental delay. We performed cytogenetic evaluation, next-generation sequencing of microdissected derivative chromosomes, and Sanger sequencing of the junction points to define the translocation's breakpoints at base pair resolution. We found that the PCDH10 and TNRC18 genes were disrupted by the breakpoints at chromosomes 4 and 7, respectively, with the formation of chimeric genes at the junction points. Gene expression studies in the patient's peripheral blood showed reduced expression of TNRC18, a gene with unknown function and clinical significance. PCDH10 plays a role in the development of the nervous system and might be involved with the patient's neurodevelopmental delay. In this study, the full molecular characterization of the junction points was shown as an efficient tool for fine breakpoint mapping in balanced translocations in order to unmask gene disruptions and investigate the potential pathogenic role of the disrupted genes.

中文翻译：

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由于平衡易位导致PCDH10和TNRC18基因中断

平衡染色体重排通常与正常表型相关，但在某些个体中，会观察到表型改变。在这些患者中，断点的分子特征可以揭示致病机制，提供疾病相关位点的注释和更好的基因型-表型相关性。在这项研究中，我们描述了一名患者，其 4q27 和 7p22 之间的平衡相互易位与神经发育延迟相关。我们进行了细胞遗传学评估、微切割衍生染色体的下一代测序和连接点的 Sanger 测序，以在碱基对分辨率下定义易位的断点。我们发现 PCDH10 和 TNRC18 基因分别被染色体 4 和 7 的断点破坏，在连接点形成嵌合基因。患者外周血中的基因表达研究显示 TNRC18 的表达降低，TNRC18 是一种功能和临床意义未知的基因。PCDH10 在神经系统的发育中发挥作用，可能与患者的神经发育迟缓有关。在这项研究中，连接点的完整分子表征被证明是平衡易位中精细断点定位的有效工具，以揭示基因中断并研究中断基因的潜在致病作用。PCDH10 在神经系统的发育中发挥作用，可能与患者的神经发育迟缓有关。在这项研究中，连接点的完整分子表征被证明是平衡易位中精细断点定位的有效工具，以揭示基因中断并研究中断基因的潜在致病作用。PCDH10 在神经系统的发育中发挥作用，可能与患者的神经发育迟缓有关。在这项研究中，连接点的完整分子表征被证明是平衡易位中精细断点定位的有效工具，以揭示基因中断并研究中断基因的潜在致病作用。