Ying Ma1, Yan Pei1, Chenghong Yin2, Yuxin Jiang3, Jingjing Wang4, Xiaofei Li4, Lin Li5, Karl Oliver Kagan6, Qingqing Wu7. 1. Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China. 2. Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China. 3. Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. 4. Department of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, 251 Yaojia Yuan Road, Chaoyang District, Beijing, 100026, China. 5. Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China. 6. Department of Women'S Health, University of Tuebingen, Tübingen, Germany. 7. Department of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, 251 Yaojia Yuan Road, Chaoyang District, Beijing, 100026, China. wuqq2007@163.com.
Abstract
PURPOSE: To analyze copy number variants (CNVs) in subjects with small for gestational age (SGA) in China. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: To analyze copy number variants (CNVs) in subjects with small for gestational age (SGA) in China. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
Entities:
Keywords:
Copy number variations; Single-nucleotide polymorphism array; Small for gestational age; Whole-genome sequencing
Authors: Nir Melamed; Ahmet Baschat; Yoav Yinon; Apostolos Athanasiadis; Federico Mecacci; Francesc Figueras; Vincenzo Berghella; Amala Nazareth; Muna Tahlak; H David McIntyre; Fabrício Da Silva Costa; Anne B Kihara; Eran Hadar; Fionnuala McAuliffe; Mark Hanson; Ronald C Ma; Rachel Gooden; Eyal Sheiner; Anil Kapur; Hema Divakar; Diogo Ayres-de-Campos; Liran Hiersch; Liona C Poon; John Kingdom; Roberto Romero; Moshe Hod Journal: Int J Gynaecol Obstet Date: 2021-03 Impact factor: 3.561