Clinical significance of copy number variations at 16p13.11-p12.3 identified by cell-free fetal DNA
10.3760/cma.j.cn113903-20240703-00486
- VernacularTitle:胎儿游离DNA检测提示16p13.11-p12.3拷贝数变异的临床价值
- Author:
Peng DAI
1
;
Ganye ZHAO
1
;
Yaqin HOU
1
;
Huanan REN
1
;
Xiangdong KONG
1
Author Information
1. 郑州大学第一附属医院遗传与产前诊断中心，郑州 450052
- Publication Type:Journal Article
- Keywords:
Cell-free fetal DNA;
16p13.11-p12.3 deletion/duplication;
Prenatal diagnosis;
Pregnancy outcome
- From:
Chinese Journal of Perinatal Medicine
2025;28(6):509-513
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the screening efficacy and clinical management strategies of cell-free fetal DNA (cffDNA) for copy number variations (CNVs) at 16p13.11-p12.3.Methods:Clinical data of 35 fetuses with high-risk indications for 16p13.11-p12.3 variations identified by non-invasive prenatal test (NIPT) at the First Affiliated Hospital of Zhengzhou University between September 2018 and December 2023 were retrospectively analyzed. Amniocentesis was performed to obtain fetal samples, followed by validation through chromosomal karyotyping and CNV-sequencing. The variant size, genetic origin, and pregnancy outcomes were systematically assessed. Statistical analysis was conducted using Pearson's Chi-square test or Fisher's exact test. Results:(1) Screening efficacy: The overall positive predictive value (PPV) of cffDNA was 45.8% (11/24), with a PPV of 4/8 for deletions and 7/16 for duplications. The false-positive rate was 54.2% (13/24), including one case complicated by a Robertsonian translocation [45,XY,rob(21;22)]. (2) Genetic characteristics: Among confirmed variants, 8/11 were inherited (six maternal duplications, one paternal deletion), while 3/11 were de novo (one deletion and two of undetermined origin). (3) Clinical outcomes: Among live births, 3/9 confirmed cases exhibited abnormal manifestations, including conductive hearing loss (one case with maternal duplication), language developmental delay (one case with 16p13.11 tetrasomy combined with trisomy), and hypotonia (one case with de novo deletion). Follow-up of false-negative or undiagnosed fetuses (22 cases) and 6/9 of confirmed cases showed no abnormalities. Conclusion:CNVs at 16p13.11-p12.3 demonstrate significant incomplete penetrance. Invasive diagnosis combined with familial analysis is recommended for cffDNA-positive cases. Genetic counseling should emphasize variant size and parental origin, and long-term neurodevelopmental follow-up mechanisms should be established for confirmed fetuses.
