Background: There is much recent interest in the biologic and diagnostic implication of cell-free non-host DNA in the plasma and serum of human subjects. To determine if quantitative abnormalities of circulating non-host DNA may be associated with certain pathologic processes, we used circulating fetal DNA in preeclampsia as a model system.
Methods: We studied 20 preeclamptic women and 20 control subjects of comparable gestational age (means, 32 and 33 weeks, respectively). Male fetal DNA in maternal serum was measured using real-time quantitative PCR for the SRY gene on the Y chromosome.
Results: The imprecision (CV) of the assay was 2.7%. The median circulating fetal DNA was increased fivefold in 20 preeclamptic women compared with 20 control pregnant women (381 vs 76 genome-equivalents/mL, P <0.001).
Conclusions: These observations suggest that preeclampsia is associated with disturbances in the liberation and/or clearance mechanisms of circulating DNA. These results also raise the possibility that measurement of circulating DNA may prove useful as a marker for the diagnosis and/or monitoring of preeclampsia.
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Clin Chem
January 2025
Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China.
Background: Mate-pair sequencing detects both balanced and unbalanced structural variants (SVs) and simultaneously informs in relation to both genomic location and orientation of SVs for enhanced variant classification and clinical interpretation, while chromosomal microarray analysis (CMA) only reports deletion/duplication. Herein, we evaluated its diagnostic utility in a prospective back-to-back prenatal comparative study with CMA.
Methods: From October 2021 to September 2023, 426 fetuses with ultrasound anomalies were prospectively recruited for mate-pair sequencing and CMA in parallel for prenatal genetic diagnosis.
Clin Chem
January 2025
Division of Maternal-Fetal-Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Background: Genetic screening has advanced from prenatal cell-free DNA (cfDNA) screening for aneuploidies (cfDNA-ANP) to single-gene disorders (cfDNA-SGD). Clinical validation studies have been promising in pregnancies with anomalies but are limited in the general population.
Methods: Chart review and laboratory data identified pregnancies with cfDNA-SGD screening for 25 autosomal dominant conditions at our academic center.
Clin Chem
January 2025
Prenatal Genomics and Therapy Section, Center for Precision Health Research, National Human Genome Institute, National Institutes of Health, Bethesda, MD, United States.
Background: Prenatal cell-free DNA (cfDNA) screening is a success story of clinical genomics that has translated to and transformed obstetric care. It is a highly sensitive and specific method of screening for the most common fetal aneuploidies, including trisomies 13, 18, and 21. While primarily designed to detect fetal chromosomal abnormalities, the test also analyzes maternal cfDNA, which can complicate interpretation of results.
View Article and Find Full Text PDFFront Pediatr
December 2024
Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Background: Autosomal recessive congenital ichthyosis (ARCI) is a group of genetic skin disorders characterized by abnormal keratinization, leading to significant health issues and reduced quality of life. ARCI encompasses harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). While all ARCI genes are linked to LI and CIE, HI is specifically associated with severe mutations in the gene.
View Article and Find Full Text PDFIntroduction: Preterm birth (PTB) is associated with newborn morbidity and mortality. DNA methylation plays an important role in the development of fetus, thus can also serve as an epigenetic biomarker. Limited epigenetic studies were conducted in regard to PTB.
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