Huanchen Yan1,2, Xiaofan Zhu3,4, Jingsi Chen1,2, Ye Cao3, Yvonne Ka Yin Kwok3, Zihan Chen4, Tak Yeung Leung3,5, Min Chen1,2, Kwong Wai Choy3,4,5. 1. Department of Fetal Medicine and Prenatal Diagnosis, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 2. Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, China. 3. Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China. 4. Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China. 5. The Chinese University of Hong Kong-Baylor College of Medicine Joint Center for Medical Genetics, Hong Kong, China.
Abstract
OBJECTIVES: To evaluate the performance of noninvasive prenatal sequencing for multiple Mendelian monogenic disorders (NIPS-M) among fetuses with skeletal abnormalities or increased nuchal translucency (NT). METHODS: Pregnancies with fetal skeletal abnormalities or increased NT (≥3.0 mm) observed by ultrasonography were recruited between October 2017 and March 2019. Parental blood from 13 couples were collected for NIPS-M testing reported. All the NIPS-M results were followed up by invasive diagnostic testing or neonatal examination. RESULTS: Among the 13 cases, 8 (61.5%) yielded positive results for pathogenic variants in the FGFR3, COL1A1, RAF1, PTPN11 and SOS1 genes by NIPS-M. One case was excluded for further analysis due to insufficient fetal DNA (<4.5%). De novo mutations were reported in six of the eight positive cases (75%). The other two were inconclusive as the pathogenic variants were detected in both plasma and genomic DNA of the mothers. The sensitivity of NIPS-M was 100%. CONCLUSIONS: Our pilot study demonstrates that NIPS-M is an accurate approach for detection of multiple monogenic disorders among fetuses with skeletal abnormalities or increased NT. It serves as an alternative and highly sensitive method to provide valuable molecular information for these groups of women who are reluctant to undergo invasive procedure.
OBJECTIVES: To evaluate the performance of noninvasive prenatal sequencing for multiple Mendelian monogenic disorders (NIPS-M) among fetuses with skeletal abnormalities or increased nuchal translucency (NT). METHODS: Pregnancies with fetal skeletal abnormalities or increased NT (≥3.0 mm) observed by ultrasonography were recruited between October 2017 and March 2019. Parental blood from 13 couples were collected for NIPS-M testing reported. All the NIPS-M results were followed up by invasive diagnostic testing or neonatal examination. RESULTS: Among the 13 cases, 8 (61.5%) yielded positive results for pathogenic variants in the FGFR3, COL1A1, RAF1, PTPN11 and SOS1 genes by NIPS-M. One case was excluded for further analysis due to insufficient fetal DNA (<4.5%). De novo mutations were reported in six of the eight positive cases (75%). The other two were inconclusive as the pathogenic variants were detected in both plasma and genomic DNA of the mothers. The sensitivity of NIPS-M was 100%. CONCLUSIONS: Our pilot study demonstrates that NIPS-M is an accurate approach for detection of multiple monogenic disorders among fetuses with skeletal abnormalities or increased NT. It serves as an alternative and highly sensitive method to provide valuable molecular information for these groups of women who are reluctant to undergo invasive procedure.
Authors: P Mohan; J Lemoine; C Trotter; I Rakova; P Billings; S Peacock; C-Y Kao; Y Wang; F Xia; C M Eng; P Benn Journal: Ultrasound Obstet Gynecol Date: 2022-01 Impact factor: 8.678