Monogenic Findings in Early Pregnancy Loss: Whole-Exome Sequencing Study of Euploid Products of Conception
References
- Bricker L, Farquharson RG. Types of pregnancy loss in recurrent miscarriage: implications for research and clinical practice. Human reproduction. 2002 May 1;17(5):1345–50.
- Bozhinovski G, Terzikj M, Kubelka-Sabit K, Jasar Dz, Lazarevski S, Livrinova V, Plaseska-Karanfilska D. Chromosomal abnormalities in early pregnancy losses:A study of 900 samples. Balkan Journal of Medical Genetics. 2024 March 08; 26(2),2023.
- Bozhinovski G, Terzikj M, Kubelka-Sabit K, Plaseska-Karanfilska D. Delineation of partial chromosomal abnormalities in early pregnancy losses. Balkan Journal of Medical Genetics. 2025;27(2):23.
- Warren JE, Silver RM. Genetics of pregnancy loss. Clinical obstetrics and gynecology. 2008 Mar 1;51(1):84–95.
- Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, Nayir A, Bakkaloğlu A, Özen S, Sanjad S, Nelson-Williams C. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proceedings of the National Academy of Sciences. 2009 Nov 10;106(45):19096–101.
- Xiao Q, Li Z, Lu J. Advances of Genetic Testing Technology in Etiology Diagnosis of Recurrent Spontaneous Abortion. Yangtze Medicine. 2023 May 6;7(2):76–86.
- Bozhinovski G, Terzikj M, Kubelka-Sabit K, Plaseska-Karanfilska D. High Incidence of CPLANE1-Related Joubert Syndrome in the Products of Conceptions from Early Pregnancy Losses. Balkan Med J. 2024 Mar 1;41(2):97–104.
- Zhao C, Chai H, Zhou Q, Wen J, Reddy UM, Kastury R, Jiang Y, Mak W, Bale AE, Zhang H, Li P. Exome sequencing analysis on products of conception: a cohort study to evaluate clinical utility and genetic etiology for pregnancy loss. Genetics in Medicine. 2021 Mar 1;23(3):435–42.
- Al Qahtani NH, AbdulAzeez S, Almandil NB, Fahad Alhur N, Alsuwat HS, Al Taifi HA, Al-Ghamdi AA, Rabindran Jermy B, Abouelhoda M, Subhani S, Al Asoom L. Whole-genome sequencing reveals exonic variation of ASIC5 gene results in recurrent pregnancy loss. Frontiers in Medicine. 2021 Jul 30;8:699672.
- Buonaiuto S, Biase ID, Aleotti V, Ravaei A, Marino AD, Damaggio G, Chierici M, Pulijala M, D’Ambrosio P, Esposito G, Ayub Q. Prioritization of putatively detrimental variants in euploid miscarriages. Scientific Reports. 2022 Feb 7;12(1):1997.
- Kline J, Vardarajan B, Abhyankar A, Kytömaa S, Levin B, Sobreira N, Tang A, Thomas-Wilson A, Zhang R, Jobanputra V. Embryonic lethal genetic variants and chromosomally normal pregnancy loss. Fertility and sterility. 2021 Nov 1;116(5):1351–8.
- Kubelka-Sabit K, Bozinovski G, Jasar D, Filipovski V, Lazarevski S, Ivanovski M, Plaseska-Karanfilska D. Detection of placental chromosomal aberrations in early spontaneous abortions in correlation with the histologic findings. Macedonian Medical Review. 2017;71(1):64–71.
- Kubelka-Sabit KB, Prodanova I, Jasar D, Bozinovski G, Filipovski V, Drakulevski S, Plaseska-Karanfilska D. Molecular and immunohistochemical characteristics of complete hydatidiform moles. Balkan journal of medical genetics: BJMG. 2017 Jun 30;20(1):27.
- Noveski P, Terzic M, Vujovic M, Kuzmanovska M, Sukarova Stefanovska E, Plaseska-Karanfilska D. Multilevel regression modeling for aneuploidy classification and physical separation of maternal cell contamination facilitates the QF-PCR based analysis of common fetal aneuploidies. Plos one. 2019 Aug 20;14(8):e0221227.
- Li, Heng. “Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM.” arXiv preprint arXiv:1303.3997 (2013).
- McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome research. 2010 Sep 1;20(9):1297–303.
- McLaren, W., Gil, L., Hunt, S.E., Riat, H.S., Ritchie, G.R., Thormann, A., Flicek, P. and Cunningham, F., 2016. The ensembl variant effect predictor. Genome biology, 17(1), pp.1–14.
- Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in medicine. 2015 May;17(5):405–23.
- Tan TY, Dillon OJ, Stark Z, Schofield D, Alam K, Shrestha R, Chong B, Phelan D, Brett GR, Creed E, Jarmolowicz A. Diagnostic impact and cost-effectiveness of whole-exome sequencing for ambulant children with suspected monogenic conditions. JAMA pediatrics. 2017 Sep 1;171(9):855–62.
- Singh AK, Olsen MF, Lavik LA, Vold T, Drabløs F, Sjursen W. Detecting copy number variation in next generation sequencing data from diagnostic gene panels. BMC Medical Genomics. 2021 Aug 31;14(1):214.
- Huang W, Zhu X, Sun G, Gao Z, Kong X. Whole-exome sequencing in deceased fetuses with ultrasound anomalies: a retrospective analysis. BMC Medical Genomics. 2023 Dec;16(1):1–2.
- Rajcan-Separovic E. Next generation sequencing in recurrent pregnancy loss-approaches and outcomes. European Journal of Medical Genetics. 2020 Feb 1;63(2):103644.
- Guo W, Zhu X, Yan L, Qiao J. The present and future of whole-exome sequencing in studying and treating human reproductive disorders. Journal of Genetics and Genomics. 2018 Oct 20;45(10):517–25.
- Robbins SM, Thimm MA, Valle D, Jelin AC. Genetic diagnosis in first or second trimester pregnancy loss using exome sequencing: a systematic review of human essential genes. Journal of Assisted Reproduction and Genetics. 2019 Aug 15;36:1539–48.
- Arnadottir GA, Jonsson H, Hartwig TS, Gruhn JR, Møller PL, Gylfason A, Westergaard D, Chan AC, Oddsson A, Stefansdottir L, Roux LL. Sequence diversity lost in early pregnancy. Nature. 2025 May 21:1–0.
- Moreno-Leon L, Quezada-Ramirez MA, Bilsbury E, Kiss C, Guerin A, Khanna H. Prenatal phenotype analysis and mutation identification of a fetus with meckel gruber syndrome. Frontiers in genetics. 2022 Aug 19;13:982127.
- Burgmaier K, Gimpel C, Schaefer F, et al. Autosomal Recessive Polycystic Kidney Disease – PKHD1. 2001 Jul 19 [Updated 2024 Apr 4]. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2026. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1326/
- Cuneo BF, Etheridge SP, Horigome H, Sallee D, Moon-Grady A, Weng HY, Ackerman MJ, Benson DW. Arrhythmia phenotype during fetal life suggests long-QT syndrome genotype: risk stratification of perinatal long-QT syndrome. Circulation: Arrhythmia and Electrophysiology. 2013 Oct;6(5):946–51.
- Killen SA, Strasburger JF. Diagnosis and management of fetal arrhythmias in the current era. Journal of Cardiovascular Development and Disease. 2024 May 24;11(6):163.
- Ali Alghamdi M, Alrasheedi A, Alghamdi E, Adly N, AlAali WY, Alhashem A, Alshahrani A, Shamseldin H, Alkuraya FS, Alfadhel M. Molecular autopsy by proxy in preconception counseling. Clinical Genetics. 2021 Dec;100(6):678–91.
- Tongsong T, Sirichotiyakul S, Chanprapaph P. Prenatal diagnosis of thrombocytopenia-absent-radius (TAR) syndrome. Ultrasound in Obstetrics and Gynecology. 2000 Mar;15(3):256–8.
- Engwerda A, Abbott KM, Hitzert MM, van Ravenswaaij-Arts CM, Kerstjens-Frederikse WS. The role of TBX18 in congenital heart defects in humans not confirmed. European Journal of Human Genetics. 2023 Feb;31(2):138–41.
- Zou M, Mangum KD, Magin JC, Cao HH, Yarboro MT, Shelton EL, Taylor JM, Reese J, Furey TS, Mack CP. Prdm6 drives ductus arteriosus closure by promoting ductus arteriosus smooth muscle cell identity and contractility. JCI insight. 2023 Mar 8;8(5):e163454.
- Padrnos L, Gangaraju R. Inherited thrombophilia and recurrent miscarriage: is there a role for anticoagulation during pregnancy?. Hematology. 2024 Dec 6;2024(1):672–7.
- Aminbeidokhti M, Halstead M, Rodriquez-Escriba M, Tise CG, Bernstein JA, Cakmak H, Pollard E, Giudice LC, Merrion K, Shaw GM, Edelman A. Genetic Variants in Recurrent Euploid Pregnancy Loss. medRxiv. 2025 Oct 3:2025–10.
- Gourhant L, Bocher O, De Saint Martin L, Ludwig TE, Boland A, Deleuze JF, Merviel P, Dupré PF, Lemarié CA, Couturaud F, Le Maréchal C. Whole exome sequencing, a hypothesis-free approach to investigate recurrent early miscarriage. Reproductive BioMedicine Online. 2021 Apr 1;42(4):789–98.
- Fu M, Mu S, Wen C, Jiang S, Li L, Meng Y, Peng H. Whole exome sequencing analysis of products of conception identifies novel mutations associated with missed abortion. Molecular medicine reports. 2018 Aug 1;18(2):2027–32.
- Byrne AB, Arts P, Ha TT, Kassahn KS, Pais LS, O’Donnell-Luria A, Babic M, Frank MS, Feng J, Wang P. Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death. Nature Medicine. 2023 Jan;29(1):180–9.
- Colley E, Hamilton S, Smith P, Morgan NV, Coomarasamy A, Allen S. Potential genetic causes of miscarriage in euploid pregnancies: a systematic review. Human reproduction update. 2019 Jul 1;25(4):452–72.
- Li J, Wang L, Ding J, Cheng Y, Diao L, Li L, Zhang Y, Yin T. Multiomics studies investigating recurrent pregnancy loss: an effective tool for mechanism exploration. Frontiers in Immunology. 2022 Apr 27;13:826198.
- Davalieva K, Terzikj M, Bozhinovski G, Kiprijanovska S, Kubelka-Sabit K, Plaseska-Karanfilska D. Comparative proteomics analysis of decidua reveals altered RNA processing and impaired ribosome function in recurrent pregnancy loss. Placenta. 2024 Sep 2;154:28–37.
- Davalieva K, Bozhinovski G, Kiprijanovska S, Kubelka-Sabit K, Plaseska-Karanfilska D. Proteomics analysis of human chorionic villi reveals dysregulated pathways that contribute to recurrent pregnancy loss.PROTEOMICS–Clinical Applications. 2024 Nov;18(6):e202400020.
- Tan TY, Lunke S, Chong B, Phelan D, Fanjul-Fernandez M, Marum JE, Kumar VS, Stark Z, Yeung A, Brown NJ, Stutterd C. A head-to-head evaluation of the diagnostic efficacy and costs of trio versus singleton exome sequencing analysis. European Journal of Human Genetics. 2019 Dec;27(12):1791–9.
DOI: https://doi.org/10.2478/bjmg-2025-00028 | Journal eISSN: 2199-5761
Language: English
Page range: 5 - 20
Published on: May 14, 2026
Published by: Macedonian Academy of Sciences and Arts
In partnership with: Paradigm Publishing Services
Publication frequency: 2 issues per year
Keywords:
Related subjects:
© 2026 Gj Bozhinovski, P Noveski, M Terzikj, K Kubelka-Sabit, D Plaseska-Karanfilska, published by Macedonian Academy of Sciences and Arts
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.