Prenatal Diagnosis Center, People's Hospital of Peking University, Beijing 100044, P.R. China.
Mol Med Rep. 2018 Feb;17(2):2811-2816. doi: 10.3892/mmr.2017.8198. Epub 2017 Dec 6.
The aim of the present study was to perform comprehensive prenatal diagnosis using various detection techniques on a fetus in a high‑risk pregnant woman, and to provide genetic counseling for the patient and her family so as to avoid birth defects. The routine karyotype analysis via amniocentesis, fluorescence in situ hybridization, and whole genome microarray technique were performed for the prenatal diagnosis of the fetus. The fetal karyotype was 46,X,ish der(X) inv(X)(p22.3q28)t(X;Y)(q28;q11.2)(XYqter+,SRY‑,DXZ1+, RP11‑64L19+,STS+,XYpter+); namely, one fetal X chromosome belonged to the derivative imbalanced chromosome and this chromosome demonstrated complex chromosomal rearrangements involving inversion, translocation and deletion. Notably, pericentric inversion between Xp22.3 and Xq28 was identified, and the chromosomal microarray technique confirmed that the long arm q28 of the derivative X chromosome had a 1.241‑Mb deletion in Xq28, which included Online Mendelian Inheritance in Man genes such as coagulation factor VIII, glucose‑6‑phosphate dehydrogenase, inhibitor of nuclear factor‑κB kinase subunit γ, trimethyllysine hydroxylase ε, Ras‑related protein Rab‑39B and chloride intracellular channel 2. In addition, this chromosome also exhibited the local translocation of fragment Yq11.21‑q11.23, which did not include the sex determining region Y gene. This fetus demonstrated deletion, inversion and translocation syndrome, and may exhibit the corresponding clinical phenotypes (e.g., intellectual disability or general delayed development) (1) of such chromosome abnormalities after birth. Therefore, in prenatal diagnosis, a variety of genetic diagnostic techniques should be comprehensively used based on specific clinical situations, which may accurately reveal the nature, sources and manifestations of the derivative chromosome abnormalities and avoid the birth of children with defects.
本研究旨在通过各种检测技术对高危孕妇胎儿进行全面产前诊断,并为患者及其家属提供遗传咨询,避免出生缺陷。对胎儿进行常规羊水细胞染色体核型分析、荧光原位杂交和全基因组微阵列技术检测,进行胎儿产前诊断。胎儿核型为 46,X,ish der(X)inv(X)(p22.3q28)t(X;Y)(q28;q11.2)(XYqter+,SRY‑,DXZ1+,RP11‑64L19+,STS+,XYpter+);即一条胎儿 X 染色体属于衍生不平衡染色体,该染色体发生复杂的染色体重排,涉及倒位、易位和缺失。值得注意的是,鉴定到 Xp22.3 和 Xq28 之间的着丝粒周围倒位,染色体微阵列技术证实,衍生 X 染色体长臂 q28 存在 Xq28 处 1.241-Mb 的缺失,该缺失包含凝血因子 VIII、葡萄糖-6-磷酸脱氢酶、核因子-κB 激酶亚单位 γ 抑制剂、三甲基赖氨酸羟化酶 ε、Ras 相关蛋白 Rab-39B 和氯离子细胞内通道 2 等在线孟德尔遗传人类基因。此外,该染色体还表现出 Yq11.21-q11.23 片段的局部易位,不包含性别决定区 Y 基因。该胎儿表现为缺失、倒位和易位综合征,出生后可能表现出此类染色体异常的相应临床表型(如智力障碍或全面发育迟缓)(1)。因此,在产前诊断中,应根据具体临床情况综合应用多种遗传诊断技术,可能准确揭示衍生染色体异常的性质、来源和表现,避免缺陷儿的出生。