Clinical Research
Genetic diagnosis of microcephaly
Liao Xiaofeng, Liao Baojian, Tan Weihe, Wang Li, Wang Dandan, Tang Erfang, Li Fuguang, Pan Xiufeng, Ji Linghua, She Qin
Published 2023-03-25
Cite as Chin J Obstet Gynecol, 2023, 58(3): 178-184. DOI: 10.3760/cma.j.cn112141-20221102-00675
Abstract
ObjectiveTo explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly.
MethodsA 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.
ResultsIn 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.
ConclusionsCMA 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.
Key words:
Microcephaly; Karyotyping; Microarray analysis; Whole exome sequencing; Prenatal diagnosis
Contributor Information
Liao Xiaofeng
Prenatal Diagnostic Center, Qingyuan People′s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China
Liao Baojian
Stem Cell and Regenerative Medicine Laboratory, Qingyuan People′s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China
Tan Weihe
Prenatal Diagnostic Center, Qingyuan People′s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China
Wang Li
Prenatal Diagnostic Center, Qingyuan People′s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China
Wang Dandan
Prenatal Diagnostic Center, Qingyuan People′s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China
Tang Erfang
Prenatal Diagnostic Center, Qingyuan People′s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China
Li Fuguang
Prenatal Diagnostic Center, Qingyuan People′s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China
Pan Xiufeng
Prenatal Diagnostic Center, Qingyuan People′s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China
Ji Linghua
Prenatal Diagnostic Center, Qingyuan People′s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China
She Qin
Prenatal Diagnostic Center, Qingyuan People′s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China
