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Low-penetrance pathogenic copy number variations (CNVs), variation of uncertain significance (VUS) CNVs and likely pathogenic CNVs present a challenge for prenatal diagnosis. Previous studies have clarified the influence of a parent-of-origin test on the prenatal VUS CNVs. However, the influence of parent-of-origin tests on prenatal likely pathogenic (LP) or low-penetrance pathogenic CNVs (pCNVs) have not been evaluated. Here, among 2273 pregnant women undergoing prenatal diagnosis, 236 CNVs were reported by chromosomal microarray analysis (CMA) including 69 full-penetrance pCNVs, 44 low-penetrance pCNVs, 113 VUS CNVs and 10 LP CNVs. Based on the subsequent parent-of-origin tests, CNVs were classified as de novo, inherited and unknown group. Firstly, a total of 112 couple (62 VUS CNVs, two LP CNVs and 48 pCNVs) chose parent-of-origin tests and 88 inherited CNVs (51 VUS CNVs, two LP CNVs and 35 pCNVs) were identified. Then, the effect of parent-of-origin tests was focused on 44 low-penetrance pCNVs, 113 VUS CNVs and 10 LP CNVs in this study (n = 167). For 44 low-penetrance pCNVs, termination of pregnancy (TOP) rates in de novo, inherited and unknown group were 100% (5/5), 23.5% (4/17) and 40.9% (9/22), respectively. TOP decisions in low-penetrance pCNVs were mainly affected by de novo and abnormal ultrasound findings. For 113 VUS CNVs, inherited VUS CNVs dramatically reduced anxiety reflected by TOP rates in de novo (18.2%, 2/11), inherited (0/51) and unknown group (2.0%, 1/51). Notably, prenatal minor structural defects often disappeared after birth. These results suggested the majority VUS CNVs have no appreciable pathogenicity. For 10 LP CNVs, TOP rates in inherited and unknown group were 0% (0/2) and 87.5% (7/8), which suggested that it is imperative that parent-of-origin tests be offered for LP CNVs to bring the classification to pathogenic or VUS. [ABSTRACT FROM AUTHOR]

Local recurrence after radiotherapy is common in locally advanced head and neck cancer (HNC) patients. Re‐irradiation can improve local disease control, but disease progression remains frequent. Hence, predictive biomarkers are needed to adapt treatment intensity to the patient's individual risk. We quantified circulating tumor DNA (ctDNA) in sequential plasma samples and correlated ctDNA levels with disease outcome. Ninety four longitudinal plasma samples from 16 locally advanced HNC patients and 57 healthy donors were collected at re‐radiotherapy baseline, after 5 and 10 radiation fractions, at irradiation end, and at routine follow‐up visits. Plasma DNA was subjected to low coverage whole genome sequencing for copy number variation (CNV) profiling to quantify ctDNA burden. CNV‐based ctDNA burden was detected in 8/16 patients and 25/94 plasma samples. Ten additional ctDNA‐positive samples were identified by tracking patient‐specific CNVs found in earlier sequential plasma samples. ctDNA‐positivity after 5 and 10 radiation fractions (both: log‐rank, p =.050) as well as at the end of irradiation correlated with short progression‐free survival (log‐rank, p =.006). Moreover, a pronounced decrease of ctDNA toward re‐radiotherapy termination was associated with worse treatment outcome (log‐rank, p =.005). Dynamic ctDNA tracking in serial plasma beyond re‐radiotherapy reflected treatment response and imminent disease progression. In five patients, molecular progression was detected prior to tumor progression based on clinical imaging. Our findings emphasize that quantifying ctDNA during re‐radiotherapy may contribute to disease monitoring and personalization of adjuvant treatment, follow‐up intervals, and dose prescription. [ABSTRACT FROM AUTHOR]

Copy number variation (CNV) is an important part of human genetic variations, which is associated with various kinds of diseases. To tackle the limitations of traditional CNV detection methods, such as restricted detection types, high error rates, and challenges in precisely identifying the location of variant breakpoints, a new method called MSCNV (copy number variations detection method for multi-strategies integration based on a one-class support vector machine model) is proposed. MSCNV establishes a multi-signal channel that integrates three strategies: read depth, split read, and read pair. First, a one-class support vector machine algorithm is used to detect abnormal signals in read depth and mapping quality values to determine the rough CNV region. Then, the rough CNV region is filtered by using paired read signals to improve the precision of MSCNV method. Finally, MSCNV explores and recognizes tandem duplication regions, interspersed duplication regions, and loss regions. It uses split read signals to determine the precise location of mutation points and to determine the type of variation. Compared with Manta, FREEC, GROM-RD, Rsicnv, and CNVkit, MSCNV significantly improves the sensitivity, precision, F1-score, and overlap density score of CNV detection while reducing the boundary bias of the detection results. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess the diagnostic efficacy of a combined approach integrating chromosomal karyotyping, copy number variation sequencing (CNV-seq), and quantitative fluorescence polymerase chain reaction (QF-PCR) in detecting chromosomal abnormalities in high-risk pregnancies. Methods: This retrospective study analyzed 617 high-risk pregnancies undergoing prenatal diagnosis from February 2023 to August 2024, with amniotic fluid samples concurrently analyzed using karyotyping, CNV-seq, and QF-PCR. We evaluated clinical characteristics, diagnostic yields, and inter-method concordance rates. Longitudinal follow-up assessed pregnancy outcomes and neonatal phenotypes, with particular emphasis on cases demonstrating diagnostic discrepancies or variants of uncertain clinical significance. Results: The integrated approach detected chromosomal abnormalities in 12.5% (77/617) of cases, significantly higher than the rates achieved by karyotyping alone (9.7%) and CNV-seq/QF-PCR alone (8.3%) (p < 0.05). Karyotyping showed full concordance with CNV-seq and QF-PCR in detecting major chromosomal aneuploidies, identifying 21 cases of trisomy 21 and 4 cases of trisomy 18. CNV-seq uniquely identified additional pathogenic copy number variations in 2.1% of cases and variants of uncertain significance (VUS) in 3.2% of cases, both undetectable by conventional karyotyping. Subjects with high-risk non-invasive prenatal testing (NIPT) results had the highest abnormality detection rate (57.6%, p < 0.05). Follow-up data revealed pregnancy termination in 44 of 97 cases with chromosomal abnormalities. Notably, neonates carrying pathogenic CNVs inherited from asymptomatic parents demonstrated normal phenotypes. Conclusion: The integration of karyotyping, CNV-seq, and QF-PCR provides superior diagnostic yield compared to individual testing strategies in high-risk pregnancies. Although karyotyping remains the gold standard for detecting major chromosomal aberrations, CNV-seq and QF-PCR enhance diagnostic precision through detection of submicroscopic variations. Multi-center studies with larger cohorts are needed to confirm these findings and clarify the clinical significance of uncertain variants. [ABSTRACT FROM AUTHOR]

Hearing loss (HL) is the most common sensory disorder, characterized by a wide range of causes, including both environmental and genetic factors. While single-nucleotide variants (SNVs) and small insertions/deletions have been extensively studied, the role of structural variations (SVs) in hearing impairment has gained increasing recognition. This review article aims to provide a comprehensive overview of the importance of SVs in HL, by exploring the SVs associated with HL and their underlying pathogenic mechanisms. Additionally, diagnostic methods of SVs have been briefly evaluated and compared in general. Three major mechanisms by which SVs can lead to HL are gene disruption, gene dosage imbalance, and position effect. Furthermore, to facilitate the detection of SVs in HL, this review presents a table highlighting the key genes and genomic regions implicated in SVs and their diagnostic approaches associated with HL patients. In the next step, indications for the use of SV diagnostic techniques are compiled in another table in this article, which will help experts in choosing the most appropriate technique. At last, the comprehensive review presented here underscores the significant role of SVs in HL. Further research is required to fully elucidate the spectrum of SVs in HL and optimize the clinical use of SV detection methods in routine diagnostic procedures. [ABSTRACT FROM AUTHOR]

Mosaic chromosomal alterations are implicated in neuropsychiatric disorders, but the contribution to schizophrenia (SCZ) risk for somatic copy number variations (sCNVs) emerging in early developmental stages has not been fully established. We analyzed blood-derived genotype arrays from 9715 patients with SCZ and 28,822 control participants of Chinese descent using a computational tool (MoChA) based on long-range chromosomal information to detect mosaic chromosomal alterations. We focused on probable early developmental sCNVs through stringent filtering. We assessed the burden of sCNVs across varying cell fraction cutoffs, as well as the frequency with which genes were involved in sCNVs. We integrated this data with the PGC (Psychiatric Genomics Consortium) dataset, which comprises 12,834 SCZ cases and 11,648 controls of European descent, and complemented it with genotyping data from postmortem brain tissue of 936 participants (449 cases and 487 controls). Patients with SCZ had a significantly higher somatic losses detection rate than control participants (1.00% vs. 0.52%; odds ratio = 1.91; 95% CI, 1.47–2.49; two-sided Fisher's exact test, p = 1.49 × 10−6). Further analysis indicated that the odds ratios escalated proportionately (from 1.91 to 2.78) with the increment in cell fraction cutoffs. Recurrent sCNVs associated with SCZ (odds ratio > 8; Fisher's exact test, p <.05) were identified, including notable regions at 10q21.1 (ZWINT), 3q26.1 (SLITRK3), 1q31.1 (BRINP3) and 12q21.31-21.32 (MGAT4C and NTS) in the Chinese cohort, and some regions were validated with PGC data. Cross-tissue validation pinpointed somatic losses at loci like 1p35.3-35.2 and 19p13.3-13.2. The study highlights the significant impact of mosaic chromosomal alterations on SCZ, suggesting their pivotal role in the disorder's genetic etiology. [ABSTRACT FROM AUTHOR]

Purpose: CTLA4 deficiency is an inborn error of immunity (IEI) due to heterozygosity for germline loss-of-function variants of the CTLA4 gene located on chromosome 2q33.2. CTLA4 deficiency underlies pleiotropic immune and lymphoproliferation-mediated features with incomplete penetrance. It has been identified in hundreds of patients but copy number variants (CNVs) have been reported in only 12 kindreds, including nine which displayed large 2q33.1-2q33.2 deletions encompassing CTLA4. Methods: We conducted a nationwide study in France to identify patients with 2q33 deletions encompassing CTLA4. We investigated the clinical and immunological phenotypes and genotypes of these patients. Results: We identified 12 patients across six unrelated kindreds with clinical immunodeficiency. Neurological features were recorded in three patients, including one with syndromic neurodevelopmental disorder. Single-nucleotide polymorphism (SNP) or comparative genomic hybridization (CGH) array analysis, and targeted high-throughput sequencing revealed five different heterozygous 2q33 deletions of 26 kilobases to 7.12 megabases in size and encompassing one to 41 genes. We identified a contiguous gene syndrome (CGS) due to associated KLF7 deficiency in a kindred with a neurodevelopmental phenotype. Conclusion: Deletions within the 2q33 region encompassing CTLA4 are rare and not extensively explored, and are probably underdiagnosed in cytogenetic practice. A literature review identified 14 different CGS loci including at least one gene responsible for an IEI. The deletions involved in IEIs should be systematically delimited, to facilitate screening for CGS. [ABSTRACT FROM AUTHOR]

Yak breeding plays a crucial role in sustaining livestock production and ensuring the livelihoods of communities in the mountainous regions of China. With the aim of improving production traits in yaks, this study explores the potential of harnessing genetic diversity and marker-assisted selection (MAS) techniques. The genetic diversity of yak populations is a valuable resource that can be tapped into to enhance desirable traits such as meat quality, milk yield, disease resistance, and adaptability to harsh environments. This study emphasizes the importance of conducting comprehensive genetic characterization of yak populations across different regions in China to identify unique genetic variations and breed-specific traits. Furthermore, the integration of MAS techniques can facilitate the selection of superior individuals for breeding programs. By identifying and utilizing genetic markers associated with desired traits, breeding strategies can be optimized, resulting in accelerated genetic improvement. Various molecular markers, such as single nucleotide polymorphisms (SNPs), microsatellites, and candidate genes, can aid in the identification of economically important traits in yaks. The availability of high-throughput genotyping technologies and advanced statistical models further support the efficient implementation of MAS in yak breeding programs. [ABSTRACT FROM AUTHOR]

Advancement in genetic testing has become increasingly important in diagnosing and managing developmental and epileptic encephalopathies (DEEs), a group of rare neurodevelopmental disorders characterized by early-onset seizures, developmental delay, and electroencephalographic (EEG) abnormalities. These early epileptic encephalopathies are often described as various syndromes as per their clearly defined, relatively uniform, and distinct clinical phenotypes with consistent EEG and/or neuroimaging findings. Finding the underlying molecular mechanisms can cause a definitive change in the management strategy. With the evolving overlapping phenotypes, advent of technologies, and discovery of new genes, it is exceedingly becoming challenging to correctly characterise these disorders and plan subsequent evidence-based management. Cytogenetic microarray (CMA) and next generation sequencing (NGS) with improved data analysis pipe-lines and algorithms have revamped the diagnostic yield dramatically. However, as of now, there is a big lacuna in step-wise evaluation guideline or consensus on integration of genetic testing results with management plan. Understanding the genetic etiologies of such syndromes timely has three major implications: (1) Knowing the outcome of such a syndrome, (2) Therapeutic implications including licensing of drugs for certain forms (e.g. genetic syndromes involving ion channels) and (3) Genetic counseling, prenatal testing and choosing reproductive options in future pregnancies in such families. The focus of this review is to provide an understanding of different types of causative variants and their step-wise genetic testing approach; the most pressing clinical need and to develop an optimal diagnostic pathway for this group of patients. [ABSTRACT FROM AUTHOR]

PurposeTo evaluate the clinical performance of expanded non-invasive prenatal testing (NIPT-plus) in screening for fetal chromosome aneuploidy and copy number variations (CNVs) among pregnant women with different risk factors to investigate how the target population of cell-free fetal DNA may change in NIPT-plus.MethodsThe clinical data, test results, confirmatory invasive testing outcomes, and follow-up results of 6,220 pregnant women who underwent NIPT-plus were re-viewed. The performance indicators of the positive predictive value (PPV), positive rate (PR), specificity, and sensitivity in screening for common trisomies, sex chromosomal abnormalities (SCAs), rare autosomal aneuploidies (RAAs), and CNVs were calculated. The PR or PPV of NIPT-plus for screening chromosome aneuploidy and CNVs in women of varying ages, risk factors, and clinical indications were determined.ResultsThe PRs of common trisomies, SCAs, RAAs, and CNVs in NIPT-plus were 0.71, 0.45, 0.32, and 0.59%, respectively, with 100% sensitivity and specificities ranging from 99.69 to 99.87%. The PPVs were 80.95, 30.77, 13.33, and 44.12%, respectively. The high-risk group had higher PRs and PPVs for chromosome aneuploidy, with no significant difference in screening for CNVs. NIPT-plus showed greater PR for aneuploidy in the older age group than in the younger age group, with no significant differences in CNVs screening.ConclusionNIPT-plus was able to effectively screen for chromosome aneuploidy and CNVs. The performance of CNVs screening was not significantly different among different risk factors and age groups. The target population for NIPT-plus should include all pregnant women, not just those at high risk.

IntroductionGenetic obesity is considered a rare disease, affecting up to 10% of patients with severe early-onset obesity. Over the past years, significant advances have been made; however, the majority of patients are misdiagnosed with polygenic obesity. Thus, this study aimed to identify deleterious copy number variations (CNVs) linked to obesity and explore the clinical phenotypes.MethodThe sample comprised 195 adults with severe obesity (BMI≥35kg/m2) who developed this phenotype during childhood or adolescence. We investigated the CNV using Multiplex Ligation-dependent Probe Amplification [MLPA] and real-time PCR. Chromosomal microarray analysis was used to assess the extent of genomic alterations.ResultsOne patient showed a ~206 kb deletion in the distal of the 16p11.2 region, encompassing twelve genes. The gene linked to the development of severe obesity was SH2B1. This alteration was found in a male patient with metabolic syndrome (MS), and hypertension. Two patients exhibited a large deletion in the proximal of the 16p11.2 region. One patient showed a ~534 kb deletion without twenty-nine genes. This female patient had hypertension and bronchitis. The other patient presented a ~598 kb deletion of the proximal 16p11.2 region, including thirty-two genes. This female patient exhibited MS, and moderate binge-eating disorder.ConclusionOur study showed three genomic deletions at the 16p11.2 region in patients with severe obesity from Brazil. These results support the clinical utility of genetic testing to identify patients with the genetic form of obesity who may benefit from specific medical treatment, family genetic counseling, and targeted therapeutic intervention.

Optical genome mapping (OGM) is an advanced technology that delivers a distinct view of genome structure. It presents numerous benefits compared to conventional sequencing techniques, as well as karyotyping in identifying large-scale structural variations (SVs). SVs refer to significant alterations in the structure of a genome that go beyond the changes of individual nucleotides. These variations can have substantial effects on gene function and are linked to various genetic diseases and disorders. There are several types of SVs, including copy number variations, such as duplications or deletions, translocations, inversions, fusions, and complex rearrangements. OGM has evolved as an innovative technology that offers high-resolution insights into genomic structures. Unlike conventional sequencing techniques such as next-generation sequencing, which concentrate on decoding short DNA segments, OGM allows for the direct visualization of long DNA strands, delivering a comprehensive, large-scale perspective of the genome’s organization. This capability makes it an effective tool for detecting SVs, which may be overlooked by other techniques. Applications of OGM are mostly in cancer genomics to detect chromosomal rearrangements and decode rare genetic disorders. OGM can also be applied in plant science, where large-scale SVs may contribute to traits such as disease. In recent years, a surge in OGM analysis has been witnessed, primarily due to the higher resolution in detecting SVs. Further, with longer reads, OGM helps in the discovery of complex and rare genomic variations.8 OGM protocol employs a paramagnetic disk designed to capture DNA during wash steps, which helps to minimize the shearing forces. Consequently, the resulting DNA fragments range from approximately 150 kilobases (kbp) to megabases (Mbp) in length, which is around 5–10 times longer than the average fragment size obtained through conventional DNA isolation techniques, making them ideal for OGM. To summarize, OGM serves as a robust technology that facilitates the direct observation of extensive SVs within the genome, offering essential insights for genomic research, clinical diagnostics, and the advancement of personalized medicine.

Introduction: Decisions concerning nuchal translucency (NT) between 3.0 and 3.4 mm remain controversial, particularly regarding whether to first calculate the combined first trimester screening test or to proceed directly with invasive testing. The literature suggests an increased risk of chromosomal aberration, as well as pathogenic copy number variations (CNVs) on chromosomal microarray, for fetuses with NT between 3.0 and 3.4 mm. The aim of this study was to describe genetic findings of fetuses with NT between 3.0 and 3.4 mm in the first trimester. The secondary objective was to describe ultrasound findings and adverse outcomes for these fetuses. The third objective was to compare genetic, ultrasound findings and adverse outcomes of fetuses with NT between 3.0 and 3.4 mm to those with NT ≥3.5 mm., Material and Methods: We conducted an observational, retrospective study in a referral center between 2017 and 2022. Genetic and ultrasound findings were compared between fetuses with NT between 3.0 and 3.4 mm and those with NT≥3.5 mm. An adverse outcome was defined as one of the following: miscarriage, perinatal death (stillbirth or neonatal death) or termination of pregnancy at parental request, and all major abnormalities or genetic disorders diagnosed before or after delivery., Results: We included 404 fetuses with NT≥3.0 mm who had invasive testing with available karyotype and chromosomal microarray, among whom 20.8% (84/404) had NT between 3.0 and 3.4 mm. The rate of adverse outcomes among fetuses with NT between 3.0 and 3.4 mm was 32.1% (27/84). The rates of chromosomal aberration, pathogenic CNVs, and major ultrasound abnormalities were 16.7% (14/84), 6.0%(5/84), and 9.2% (6/65), respectively, for fetuses with NT between 3.0 and 3.4 mm. In comparison, fetuses with NT greater than 3.5 mm had higher rates of chromosomal aberration and major ultrasound abnormalities, with rates of 47.5% (152/320) and 30.2% (49/162) respectively compared to 16.7% (14/84) and 9.2% (6/65) for fetuses with NT between 3.0 and 3.4 mm (p < 0.001 for both comparisons). However, the rate of pathogenic CNVs was not significantly different between the two groups, with rates of 1.9% (6/320) for NT≥3.5 mm and 6.0% (5/84) for NT between 3.0 and 3.4 mm (p = 0.06)., Conclusions: The rate of chromosomal aberration and pathogenic CNVs on chromosomal microarray is high among fetuses with NT between 3.0 and 3.4 mm, although these rates remain lower than those observed among fetuses with NT≥3.5 mm., (© 2025 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

We examine the complex relationship between genomic copy number variation (CNV) and gene expression, highlighting the relevance to cancer biology and other biological contexts. By tracing the history of genometranscriptome correlations, we emphasize the complexity and challenges in understanding these interactions, particularly within the heterogeneous landscape of human cancers. Recent advances in computational algorithms and high-throughput single-cell multi-omic sequencing technologies are discussed, demonstrating their potential to refine our understanding of cancer biology and their limitations. The integration of genomic and transcriptomic analyses, which offers novel insights into tumor evolution and heterogeneity as well as therapeutic strategies, is presented as a crucial approach for advancing cancer research., (© 2025 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.)

Background: Recent research elucidated the prognostic significance of molecular biology in Wilms tumor (WT) by linking somatic genomic variants (such as gain of chromosome 1q) to unfavorable patient outcomes. This analysis describes the clinical impact of copy number variations (CNV) in tumor samples of WT patients with stage IV disease., Methods: Tumor samples of 55 WT patients with stage IV disease from the United Kingdom, France, and Germany enrolled in the SIOP 2001 study and treated with preoperative chemotherapy (pCHT) were examined for their CNVs of chromosome 1q and other regions of interest using multiplex ligation-dependent probe amplification (MLPA). The identified CNV were analyzed regarding their prognostic impact., Results: Chromosome 1q gain (1q+) and TP53 loss occurred in 38.2% and 16.4% of tumors and were associated with older patient age at diagnosis (median [months]: 65 and 64 vs. 49 each, p = 0.03 and 0.02, respectively) and poorer 5-year event-free survival (40.0% and 11.1% vs. 67.7% and 82.6%, p = 0.04 and <0.01, respectively) compared to their specific control group of tumors without the respective CNV. In patients with pulmonary-only metastasis, 1q+ was an adverse prognostic marker irrespective of remission status after pCHT with or without metastasectomy. A simultaneous MYCN gain occurred more frequently in tumors with 1q+ than in tumors without 1q+ (p = 0.03). TP53 loss was linked to high-risk histology and inferior 5-year overall survival (p < 0.001)., Conclusions: We confirm the prognostic relevance of 1q+ and TP53 loss in stage IV WTs and emphasize their potential utility for future treatment stratification., (© 2025 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

This study aimed to identify the chromosomal anomalies and copy number variations (CNVs) in autism spectrum disorder (ASD) and to provide genotype/phenotype correlations. Fifty-four patients diagnosed with ASD between March 2021 and June 2022 were included in the study. Patients were evaluated by cytogenetic analysis and array comparative genomic hybridisation analysis (aCGH). The structural and numerical chromosomal anomaly was detected in 3.7%, and the CNVs were identified in 18.52% of patients. Of the CNVs detected, 27.3% were identified as pathogenic, 18.2% as likely pathogenic and 54.5% as VUS. The copy number gain rate of the detected CNVs was higher than the copy number losses rate, 70% and 30% respectively. As an important finding in the study, a new pathogenic CNV with a 6.3-mb copy number gain in the 3p22.3p22.2 region, whose gene region had not been previously defined in OMIM, was detected. Identifying a genetic aetiology may provide clinicians with more information about disease prognosis and risk of recurrence., (© 2024 International Society for Developmental Neuroscience.)

Objective: To report a rare 17q12 microduplication family., Case Report: A 29-year-old woman (gravida 1, para 0) underwent amniocentesis at 21 weeks' gestation because of double bubble sign and polyhydramnios of the fetus on prenatal ultrasound. Chromosomal microarray analysis (CMA) from this family revealed a 1.78-Mb microduplication on chromosome 17q12 of the fetal, spanning from position 34,460,444 to 36,243,365 (GRCh37). Trio whole-exome sequencing (WES) showed 17q12 microduplication in the fetal and the mother. After genetic counselling and being informed of the unfavourable prognosis, the parents decided to continue the pregnancy., Conclusion: We provide a detailed description of the phenotype in a rare family with 17q12 microduplication. Combination of karyotype analysis, CMA, WES, prenatal ultrasound and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background and Objects: Intrauterine growth restriction (IUGR) is a common and complex obstetricsc condition, especially when accompanied by congenital abnormalities. The aim of this research is to diagnose the genetic abnormalities in IUGR fetuses with malformation on ultrasound., Subjects and Methods.: Cross-sectional descriptive study performed from 2021 to 2023 at the Prenatal diagnosis center of National Hos-pital of Obstetric and Gynecology, collected total of 129 cases IUGR suitable for research., Results: The average gestational age at which growth restriction was 25.40 ± 4.86 weeks, IUGR fetuses often accompanied malformations, most of them belong to the cardiovascular system, 75 cases undergoing amniocentesis for karyotyping and SNP Array testing to examine genetic abnormalities. There were 26 cases detected with genetic abnormalities, including 8 cases by both methods, 16 cases with positive Array but negative karyotype, Array SNP can detect twice the number of cases that could be missed, 16 pathogenic copy number variations (CNVs) including gains and deletions, related to some specific clinical syndromes., Conclusion: CMA technology shows quite effective application value in determining genetic causes of IUGR and Array SNP should be recommended for use.