Department of Genetics and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Ultrasound Obstet Gynecol. 2019 Nov;54(5):655-660. doi: 10.1002/uog.20230.
Chromosomal microarray analysis (CMA) is the modality of choice for prenatal diagnosis in pregnancy with fetal malformation, as it has a high diagnostic yield for microdeletion/duplication syndromes. The aim of this study was to demonstrate the additional utility of single-nucleotide polymorphism (SNP)-based CMA in diagnosing monogenic diseases, imprinting disorders and uniparental disomy (UPD).
CMA was performed using Affymetrix CytoScan array, for all indications in 6995 pregnancies, at a tertiary referral hospital from November 2013 to June 2018. We describe four cases that had a CMA result that provided a more comprehensive understanding of the complex genetic mechanisms underlying the clinical presentation.
In the first fetus, CMA was performed due to intrauterine growth restriction and revealed a 75 kbp maternally inherited microdeletion encompassing the Bloom syndrome gene (BLM). A diagnosis of Bloom syndrome was made upon identifying a paternally inherited common Ashkenazi founder mutation. In the second case, CMA was performed due to severely abnormal maternal serum analytes and revealed a deletion in 14q32.2q32.31 on the maternally inherited copy, leading to a diagnosis of Kagami-Ogata syndrome, which is an imprinting disorder. In the third case, amniocentesis was performed because of late-onset fetal macrosomia and mild polyhydramnios. CMA detected a deletion encompassing the locus of Prader-Willi/Angelman syndrome. In the fourth case, amniocentesis was performed due to maternal cytomegalovirus seroconversion. Maternal UPD of the entire long arm of chromosome 11 was detected.
Prenatal CMA, based on oligo and SNP platforms, increases the diagnostic yield and enables a wider spectrum of disorders to be detected through the identification of complex genetic etiologies beyond only copy number variants. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
染色体微阵列分析（CMA）是胎儿畸形妊娠产前诊断的首选方法，因为它对微缺失/重复综合征具有较高的诊断率。本研究旨在证明基于单核苷酸多态性（SNP）的 CMA 可用于诊断单基因疾病、印迹障碍和单亲二体（UPD）。
2013 年 11 月至 2018 年 6 月，在一家三级转诊医院，对 6995 例妊娠进行了所有适应症的 Affymetrix CytoScan 阵列 CMA。我们描述了 4 例 CMA 结果，这些结果更全面地了解了临床表型背后的复杂遗传机制。
第一例胎儿因宫内生长受限而行 CMA，结果显示 75kbp 母系微缺失，包含布卢姆综合征基因（BLM）。在识别出父系遗传的常见阿什肯纳兹创始人突变后，诊断为布卢姆综合征。第二例因严重异常的母体血清分析物而行 CMA，结果显示母系拷贝的 14q32.2q32.31 缺失，导致卡加米-奥加塔综合征的诊断，这是一种印迹障碍。第三例因晚发胎儿巨大儿和轻度羊水过多而行羊膜穿刺术。CMA 检测到涵盖 Prader-Willi/Angelman 综合征基因座的缺失。第四例因母体巨细胞病毒血清转化而行羊膜穿刺术。检测到整个 11 号染色体长臂的母体 UPD。
基于寡核苷酸和 SNP 平台的产前 CMA 增加了诊断率，并通过识别超出拷贝数变异的复杂遗传病因，使更广泛的疾病谱得以检测。版权所有 © 2019 ISUOG。由 John Wiley & Sons Ltd 出版。
