Satkin N B, Karaman B, Ergin S, Kayserili H, Kalelioglu I H, Has R, Yuksel A, Basaran S
Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul, Turkey.
Balkan J Med Genet. 2021 Mar 23;23(2):25-34. doi: 10.2478/bjmg-2020-0026. eCollection 2020 Nov.
Carriers of apparently balanced chromosomal rearrangements (ABCRs) have a 2-3-fold higher risk of carrying an abnormal phenotype, when compared to the average population. Apparently balanced chromosomal rearrangements can be imbalanced at the submicroscopic level, and changes in the gene structure, formation of a new chimeric gene, gain or loss of function of the genes and altered imprinting pattern may also affect the phenotype. Chromosomal microarray (CMA) is an efficient tool to detect submicroscopic imbalances at the breakpoints as well as in the whole genome. We aimed to determine the effectiveness of array-comparative genomic hybridization (aCGH) application in phenotypically affected cases with ABCRs at a single center from Turkey. Thirty-four affected cases (13 prenatal, 21 postnatal) carrying ABCRs were investigated with CMA. In postnatal series, ABCRs were familial in 7 and in 14 cases. Seven cases were imbalanced (in postnatal series 33.3% and in cases 50.0%). Out of 13 prenatal cases, five were familial and eight were in origin and two cases were imbalanced (in 15.4% prenatal series and in 25.0% cases). No cryptic imbalance was observed in familial cases. The anomaly rates with array studies ranged between 14.3-25.0% in familial and between 20.0-57.5% in cases of postnatal series in the literature. Studies focused on prenatal ABCR cases with abnormal ultrasound findings are limited and no submicroscopic imbalance was reported in the cohorts. When postnatal or prenatal results were combined, the percentage of abnormalities detected by CMA was 40.9%. Taking this contribution into consideration, all ABCRs should be investigated by CMA even if the fetal ultrasound findings are normal.
与普通人群相比,明显平衡的染色体重排(ABCR)携带者出现异常表型的风险要高2至3倍。明显平衡的染色体重排可能在亚微观水平上出现失衡,基因结构的改变、新嵌合基因的形成、基因功能的获得或丧失以及印记模式的改变也可能影响表型。染色体微阵列(CMA)是检测断点处以及全基因组中亚微观失衡的有效工具。我们旨在确定在土耳其一个单一中心对有ABCR且有表型影响的病例应用阵列比较基因组杂交(aCGH)的有效性。对34例携带ABCR的受累病例(13例产前,21例产后)进行了CMA研究。在产后病例系列中,7例ABCR为家族性,14例为散发性。7例出现失衡(产后病例系列中为33.3%,散发性病例中为50.0%)。在13例产前病例中,5例为家族性,8例为散发性,2例出现失衡(产前病例系列中为15.4%,散发性病例中为25.0%)。家族性病例中未观察到隐匿性失衡。文献中家族性病例的阵列研究异常率在14.3%至25.0%之间,产后病例系列的散发性病例中在20.0%至57.5%之间。针对有异常超声表现的产前ABCR病例的研究有限,且队列研究中未报告亚微观失衡情况。当将产后和产前结果合并时,CMA检测到的异常百分比为40.9%。考虑到这一贡献,即使胎儿超声检查结果正常,所有ABCR病例都应通过CMA进行研究。