Subchromosomal anomalies in small for gestational-age fetuses and newborns
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To analyze copy number variants (CNVs) in subjects with small for gestational age (SGA) in China.
A total of 85 cases with estimated fetal weight (EFW) or birth weight below the 10th percentile for gestational age were recruited, including SGA associated with structural anomalies (Group A, n = 20) and isolated SGA (Group B, n = 65). In all cases, cytogenetic karyotyping and infection screening were normal. We examined DNA from fetuses (amniocentesis or cordocentesis) and newborns (cord blood) to detect CNVs using a single nucleotide polymorphism (SNP, n = 75) array or low-pass whole-genome sequencing (WGS, n = 10).
Of 85 total cases, 3 (4%) carried pathogenic chromosomal abnormalities, including 2 cases with pathological CNVs and 1 case with upd(22)pat. In Group A, the mean gestational age at the time of diagnosis was 26.8 (SD 4.1) weeks and mean EFW/birth weight was 907.2 (SD 567.8) g. In Group B, the mean gestational age at the time of diagnosis was 34.1 (SD 5.8) weeks. Mean EFW/birth weight was 1879.2 (SD 714.5) g. The pathologic detection rate was 10% (2/20) in Group A and 2% (1/65) in Group B. It was inclined that the lower the EFW percentile, the more frequent the occurrence of CNVs.
Pathological subchromosomal anomalies were detected by CMA or low-pass WGS in 10% and 2% of SGA subjects with and without malformation, respectively. SGA fetuses with structural anomalies presented with higher pathological subchromosomal anomalies. The molecular genetic analysis is not recommended for isolated SGA pregnancies without other abnormal findings.
KeywordsCopy number variations Small for gestational age Single-nucleotide polymorphism array Whole-genome sequencing
Protocol/project development and study design: YM, CY and QW; drafting of the study and revision for important intellectual content: KOK, YJ, CY and LL; data collection: YM, YP and XL; data analysis and interpretation: YM and JW; manuscript writing/editing: YM; KOK; substantial contributions to the study conception: QW; final approval of the version to be published: YM and QW.
This study was supported by the National Key Research and Development Program of China (Grant No. 2016YFC1000104 and 2016YFC1000101), Beijing Municipal Administration of Hospitals’ Ascent Plan (Grant No. DFL20151302), and National Science and Technology Infrastructure Program (Grant No. 2014BAI06B05).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This study was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital and was in accordance with the 1964 Helsinki Declaration and its later amendments.
Each participant in this study signed an informed consent form.
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