Xu Zhiyong, Geng Qian, Luo Fuwei, Xu Fang, Li Peining, Xie Jiansheng
Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, Guangdong China.
Department of Genetics, Yale University School of Medicine, New Haven, CT USA.
Mol Cytogenet. 2014 Dec 9;7(1):84. doi: 10.1186/s13039-014-0084-5. eCollection 2014.
The aims of this study were to evaluate the clinical utility of multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH) analyses on prenatal cases and to review prenatal ultrasound findings of cytogenomic syndromes.
Of the 54 prenatal cases analyzed, cytogenomic abnormalities were characterized in 14 cases. In four fetuses with abnormal ultrasound findings, a 40.701 Mb duplication of 8q22.3-q24.3 and a 23.839 Mb deletion of 7q33-q36.3 derived from a paternal balanced translocation, a de novo 13.062 Mb deletion of 11q24.1-q25 for Jacobsen syndrome, a de novo 19.971 Mb deletion of 7q11.23-q21.3 for type 1 split-hand/foot malformation (SHFM1), and a de novo 28.909 Mb duplication of 3q21.1-q25.1 were detected. A 699.8 Kb deletion at 5p15.33 for Cri du Chat syndrome was confirmed in a fetus with abnormal MLPA result. A fetus with abnormal maternal screening was detected with a de novo distal 1.747 Mb duplication at 2q37.1-q37.2 and a 6.664 Mb deletion at 2q37.2-q37.3. Of the eight cases referred by history of spontaneous abortions, derivative chromosomes 11 from paternal carriers of a balanced 8q/11q and a 10q/11q translocation were noted in two cases, simple aneuploids of trisomy 2 and trisomy 21 were seen in three cases, and compound aneuploids of two or three chromosomes were found in three cases. Post-test genetic counseling was performed with detailed genomic information and well characterized postnatal syndromic features.
These results demonstrated that coupling MLPA screening and aCGH analysis are a cost-effective approach to detect cytogenomic abnormalities in a prenatal setting. The aCGH analysis provided not only genomic maps of breakpoints and gene content of imbalanced regions but also better inference of related phenotypes for genetic counseling. Prenatal ultrasound findings reported in the literature for Jacobsen syndrome, SHFM and Cri du Chat syndrome were summarized for use as diagnostic references.
本研究的目的是评估多重连接依赖探针扩增（MLPA）和阵列比较基因组杂交（aCGH）分析在产前病例中的临床应用，并回顾细胞基因组综合征的产前超声检查结果。
在分析的54例产前病例中，14例具有细胞基因组异常特征。在4例超声检查结果异常的胎儿中，检测到源自父系平衡易位的8q22.3 - q24.3区域40.701 Mb的重复和7q33 - q36.3区域23.839 Mb的缺失、雅各布森综合征（Jacobsen syndrome）的11q24.1 - q25区域13.062 Mb的新发缺失、1型裂手裂足畸形（SHFM1）的7q11.23 - q21.3区域19.971 Mb的新发缺失以及3q21.1 - q25.1区域28.909 Mb的新发重复。在MLPA结果异常的胎儿中确诊了5p15.33区域699.8 Kb的缺失，该缺失导致猫叫综合征（Cri du Chat syndrome）。在1例母亲筛查异常的胎儿中检测到2q37.1 - q37.2区域1.747 Mb的新发远端重复和2q37.2 - q37.3区域6.664 Mb的缺失。在8例有自然流产史转诊的病例中，2例发现了来自8q/11q和10q/11q平衡易位父系携带者的衍生染色体11，3例出现了21 - 三体和2 - 三体的单纯非整倍体，3例发现了两到三条染色体的复合非整倍体。利用详细的基因组信息和特征明确的产后综合征特征进行了检测后遗传咨询。
这些结果表明，联合MLPA筛查和aCGH分析是在产前检测细胞基因组异常的一种经济有效的方法。aCGH分析不仅提供了不平衡区域断点的基因组图谱和基因内容，还为遗传咨询提供了更好的相关表型推断。总结了文献中报道的雅各布森综合征、SHFM和猫叫综合征的产前超声检查结果，以供诊断参考。
