Czakó Márta, Szabó András, Till Ágnes, Zsigmond Anna, Hadzsiev Kinga
Department of Medical Genetics, Medical School, University of Pécs, 7624 Pécs, Hungary.
Int J Mol Sci. 2025 Sep 12;26(18):8886. doi: 10.3390/ijms26188886.
Complex chromosomal rearrangements (CCRs) are rare structural abnormalities involving at least three chromosomal breakpoints and often two or more chromosomes. Owing to their inherent genomic complexity, CCRs are frequently associated with abnormal phenotypes, including developmental delay, congenital anomalies, and infertility. In this study, we report four male patients, three of them with de novo rare structural chromosomal rearrangement detected through a combination of Giemsa-Trypsin (GTG) banding, fluorescence in situ hybridization (FISH), and high-resolution microarray techniques (SNP array and array CGH). Each of the four cases turned out to be of a different type: in addition to two exceptional CCRs, an inv dup del 18q and a cluster rearrangement involving the long arm of chromosome 4 were identified. Despite the limitations of the testing methods, we performed a detailed analysis of the relationship between the most detailed genotype data and the associated phenotype. Our study provides further valuable evidence that the use of molecular cytogenetic methods is of paramount importance even in cases with abnormal karyotypes detected by light microscopy, as high-resolution data may reveal unsuspected genomic complexity, which is essential for genetic counseling in these patients.
复杂染色体重排（CCRs）是罕见的结构异常，涉及至少三个染色体断点，且常涉及两条或更多条染色体。由于其固有的基因组复杂性，CCRs常与异常表型相关，包括发育迟缓、先天性异常和不育。在本研究中，我们报告了四名男性患者，其中三名通过吉姆萨 - 胰蛋白酶（GTG）显带、荧光原位杂交（FISH）和高分辨率微阵列技术（SNP阵列和阵列比较基因组杂交）的组合检测到新生的罕见结构染色体重排。这四个病例中的每一个都属于不同类型：除了两个特殊的CCRs外，还鉴定出一个inv dup del 18q和一个涉及4号染色体长臂的簇状重排。尽管检测方法存在局限性，但我们对最详细的基因型数据与相关表型之间的关系进行了详细分析。我们的研究提供了进一步的重要证据，即即使在通过光学显微镜检测到核型异常的病例中，使用分子细胞遗传学方法也至关重要，因为高分辨率数据可能揭示未被怀疑的基因组复杂性，这对这些患者的遗传咨询至关重要。
