Liao X F, Liao B J, Tan W H, Wang L, Wang D D, Tang E F, Li F G, Pan X F, Ji L H, She Q
Prenatal Diagnostic Center, Qingyuan People's Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China.
Stem Cell and Regenerative Medicine Laboratory, Qingyuan People's Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China.
Zhonghua Fu Chan Ke Za Zhi. 2023 Mar 25;58(3):178-184. doi: 10.3760/cma.j.cn112141-20221102-00675.
To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly. A total of 9 cases of microcephaly fetuses diagnosed by prenatal ultrasound or children with microcephaly diagnosed after birth were selected from the Sixth Affiliated Hospital of Guangzhou Medical University from January 2014 to August 2022.Karyotype analysis and/or CMA were used to detect. The cases with negative karyotype analysis and CMA results were further sequenced by trio-based WES (Trio-WES). Then the coding genes contained in the pathogenic copy number variation (CNV) fragments were analyzed by gene ontology (GO) enrichment. The genes related to the development of the central nervous system contained in the pathogenic CNV and the pathogenic genes found by Trio-WES were combined for gene interaction network analysis. In this study, 9 cases of microcephaly were recruited, with the time of diagnosis ranged from 23 weeks of gestation to 7 years after birth, and the head circumference of fetus or children ranged from 18.3 to 42.5 cm (-7SD to -2SD). Karyotype analysis was detected in all 9 cases and no abnormality result was found. Eight cases were detected by CMA, and one abnormal was found. Five cases were detected by Trio-WES, and two cases were detected with likely pathogenic genes. The GO enrichment analysis of the coding gene in the 4p16.3 microdeletion (pathogenic CNV) region showed that: in biological process, it was mainly concentrated in phototransduction, visible light; in terms of molecular function, it was mainly concentrated in fibroblast growth factor binding; in terms of cell components, it was mainly concentrated in rough endoplasmic reticulum. Gene interaction network analysis suggested that CDC42 gene could interact with CTBP1, HTT and ASPM gene. CMA could be used as a first-line detection technique for microcephaly. When the results of chromosome karyotype analysis and/or CMA are negative, Trio-WES could improve the detection rate of pathogenicity of microcephaly.
探讨染色体核型分析、染色体微阵列分析（CMA）及全外显子组测序（WES）在小头畸形中的诊断价值。选取2014年1月至2022年8月在广州医科大学附属第六医院诊断的9例产前超声诊断的小头畸形胎儿或出生后诊断的小头畸形患儿。采用核型分析和/或CMA进行检测。核型分析和CMA结果为阴性的病例进一步采用三联体全外显子组测序（Trio-WES）。然后通过基因本体（GO）富集分析致病拷贝数变异（CNV）片段中包含的编码基因。将致病CNV中与中枢神经系统发育相关的基因和Trio-WES发现的致病基因进行基因相互作用网络分析。本研究共纳入9例小头畸形患者，诊断时间从妊娠23周至出生后7年，胎儿或儿童的头围范围为18.3至42.5 cm（-7SD至-2SD）。9例均进行了核型分析，未发现异常结果。8例进行了CMA检测，发现1例异常。5例进行了Trio-WES检测，2例检测到可能的致病基因。对4p16.3微缺失（致病CNV）区域的编码基因进行GO富集分析显示：在生物学过程方面，主要集中在光转导、可见光；在分子功能方面，主要集中在成纤维细胞生长因子结合；在细胞成分方面，主要集中在粗面内质网。基因相互作用网络分析表明，CDC42基因可与CTBP1、HTT和ASPM基因相互作用。CMA可作为小头畸形的一线检测技术。当染色体核型分析和/或CMA结果为阴性时，Trio-WES可提高小头畸形致病性的检测率。
