A single-centre study from northeastern Türkiye has documented what a multimodal prenatal genetic testing pathway actually delivered in a regional maternity service, and the results carry a sobering message about how much trust a high-risk screening result deserves. Researchers at Ordu University Training and Research Hospital analysed 120 consecutive amniocenteses performed between March 2022 and June 2025, covering every invasive procedure carried out at the department over a 40-month period without exclusions. The retrospective cohort, published in BMC Medical Genomics, offers a rare window into prenatal genomics outside high-volume referral centres, where most published evidence on chromosomal microarray analysis and exome sequencing originates.
The cohort produced an overall abnormal finding rate of 30.0 percent, with abnormalities identified in 36 of the 120 pregnancies. Twenty-seven pregnancies, or 22.5 percent, carried disease-causing findings: 16 autosomal aneuploidies, one sex chromosome aneuploidy, seven pathogenic or likely pathogenic copy-number variants and three single gene disorders. A further nine pregnancies, 7.5 percent, had incidental or non-diagnostic findings, comprising three heterozygous pathogenic variants in autosomal recessive genes, which mark the fetus as a carrier, and six variants of uncertain significance. The authors classified findings before analysis into these two categories to avoid inflating the apparent burden of fetal disease, since carrier findings and uncertain variants do not cause disease in the fetus.
The diagnostic pathway was observed retrospectively rather than implemented prospectively, and this distinction shapes every number in the study. The intended first-tier panel combined quantitative fluorescent PCR, G-banded chromosome analysis and chromosomal microarray analysis, but all three tests were completed in only 94 pregnancies, or 78.3 percent. Microarray was performed in 101 pregnancies, 84.2 percent, while exome sequencing was applied selectively in just 13 cases and targeted testing in 25. Tests were requested according to indication, sample quality, turnaround requirements and earlier results, reflecting routine clinical practice rather than a fixed protocol.
Against this uneven backdrop, the additional modalities still changed what could be told to parents. Conventional cytogenetics, meaning quantitative fluorescent PCR and G-banded karyotyping, identified 20 disease-causing diagnoses, a cumulative yield of 16.7 percent. Microarray then resolved four further pathogenic copy-number variants that conventional methods could not detect, and sequencing or targeted analyses identified three single gene disorders, bringing the final disease-causing yield to 27 of 120 pregnancies. Seven of the 27 diagnoses, 25.9 percent, were first identified by microarray, exome sequencing or targeted testing and would have been missed by conventional cytogenetics alone. Because these modalities were not applied uniformly, the authors stress that this figure describes the contribution observed in this specific cohort rather than an estimate of diagnostic yield.
The three single gene disorders illustrate the reach of sequencing in selected cases. Targeted TCOF1 sequencing diagnosed Treacher Collins syndrome in a pregnancy referred because the mother was affected. Exome sequencing identified compound heterozygous PSAT1 variants causing phosphoserine aminotransferase deficiency and a homozygous UNC13D genotype causing familial haemophagocytic lymphohistiocytosis type 3. Among the copy-number findings were a 4p16.3 deletion causing Wolf-Hirschhorn syndrome, a 16p11.2 deletion, and a recurrent 1.7 Mb Xp22.31 deletion encompassing the STS gene associated with X-linked ichthyosis.
Perhaps the most practically consequential results concern non-invasive prenatal testing. Fourteen pregnancies were referred after a high-risk NIPT result from external commercial laboratories, and confirmatory amniocentesis told a sharply target-dependent story. All six referrals for trisomy 21 or trisomy 18 were confirmed, a rate of six out of six. Not one of the four calls for sex chromosome aneuploidies or rare autosomal trisomies was confirmed. Of four NIPT-reported copy-number variants, only the 4p microdeletion was confirmed as Wolf-Hirschhorn syndrome. The authors emphasise that these are confirmation rates within a referral stream, not population-level positive predictive values, and the confidence intervals are wide and overlapping. Even so, the pattern reinforces that a high-risk NIPT result should be diagnostically confirmed before any irreversible clinical decision, particularly for less common targets.
Ultrasound findings also shaped yield. Abnormal ultrasonography was associated with an abnormal genetic finding overall, present in 31 of 83 pregnancies with abnormal imaging versus 5 of 37 with normal imaging, giving an unadjusted odds ratio of 3.82. When restricted to disease-causing findings alone, the association pointed in the same direction but did not reach statistical significance. Notably, a normal ultrasound did not exclude a chromosomal diagnosis: four disease-causing findings occurred in pregnancies with normal imaging, including two cases of trisomy 21. The authors caution that these unadjusted estimates describe association rather than causation.
Pregnancy outcomes were ascertained only for pregnancies in which an abnormal finding had been reported, a structural feature of the service, and were documented in 30 of the 36 abnormal cases. Among these, 22 pregnancies, 73.3 percent, were terminated and eight resulted in live birth. Termination frequencies varied markedly by diagnostic category: all four trisomy 18 pregnancies were terminated, nine of 11 trisomy 21 pregnancies, four of seven pathogenic copy-number variants, but only one of six pregnancies whose sole finding was a variant of uncertain significance and one of three carrier findings. The single 47,XXX pregnancy resulted in live birth. The authors insist these descriptive differences be read in the context of fetal phenotype, diagnostic certainty, parental preferences and the legal and cultural setting.
The study also documents the realities of regional practice. Mean gestational age at amniocentesis was 18.1 weeks, and 21.7 percent of procedures were performed beyond 20 weeks, mostly reflecting delayed referral. Four procedures were deliberately carried out before 15 completed weeks at the parents’ request after first-trimester anomaly findings, a departure from recommended timing that was discussed and consented to in each case. Mean maternal age was 31.5 years, and nearly half of the trisomy 21 cases occurred in women younger than 35, supporting screening irrespective of age.
The limitations are substantial and the authors state them plainly. The design is retrospective and single-centre with a modest sample. Exome sequencing was applied to a clinically selected subgroup, so no yield estimate for universal sequencing can be drawn. Outcome follow-up covered only the abnormal-finding group, so no cohort-wide outcome rate is estimated. NIPT platform metadata were non-uniform, post-amniocentesis complications were not systematically recorded, and laboratory quality assurance could be documented only from issued reports. Even so, the study delivers a service-level message with real weight: a moderate-volume regional centre delivered most components of a multimodal genomic pathway, additional testing tiers changed what could be said to parents, and confirmatory invasive testing remains essential before irreversible decisions rest on a screening result.
Subject of Research: Multimodal genomic testing and NIPT confirmation in 120 prenatal amniocenteses at a regional Turkish centre
Article Title: Multimodal genomic testing in prenatal diagnosis: incremental diagnostic contribution of chromosomal microarray and exome sequencing, real-world NIPT confirmation rates and pregnancy outcomes in 120 consecutive amniocenteses from northeastern Türkiye — a retrospective cohort study
Article References: Doğan, Ç., Atalay, S., & Timur, H. (2026). Multimodal genomic testing in prenatal diagnosis: incremental diagnostic contribution of chromosomal microarray and exome sequencing, real-world NIPT confirmation rates and pregnancy outcomes in 120 consecutive amniocenteses from northeastern Türkiye — a retrospective cohort study. BMC Medical Genomics, 19(1), Article 153. https://doi.org/10.1186/s12920-026-02491-7
Image Credits: AI Generated
DOI: 10.1186/s12920-026-02491-7
Keywords: prenatal diagnosis, chromosomal microarray, exome sequencing, NIPT, amniocentesis, copy-number variants, aneuploidy, variants of uncertain significance, Türkiye, retrospective cohort, pregnancy outcomes, genetic counselling
News Source: Juliet Wilcox. (October 30, 2026). Regional prenatal genomic testing adds diagnoses, but NIPT confirmations vary sharply. Scienmag.
