Diagnostics

Research

16 pages, 7325 KiB

Open AccessArticle

Detection of Mosaic Absence of Heterozygosity (AOH) Using Low-Pass Whole Genome Sequencing in Prenatal Diagnosis: A Preliminary Report

by Yan Lü, Yulin Jiang, Xiya Zhou, Na Hao, Chenlu Xu, Ruidong Guo, Jiazhen Chang, Mengmeng Li, Hanzhe Zhang, Jing Zhou, Wei (Victor) Zhang and Qingwei Qi

Diagnostics 2023, 13(18), 2895; https://doi.org/10.3390/diagnostics13182895 - 9 Sep 2023

Cited by 2 | Viewed by 1517

Abstract

Objective: Mosaicism is a common biological phenomenon in organisms and has been reported in many types of chromosome abnormalities, including the absence of heterozygosity (AOH). Due to the detection limitations of the sequencing approach, mosaic AOH events are rarely assessed in clinical [...] Read more.

Objective: Mosaicism is a common biological phenomenon in organisms and has been reported in many types of chromosome abnormalities, including the absence of heterozygosity (AOH). Due to the detection limitations of the sequencing approach, mosaic AOH events are rarely assessed in clinical cases. Herein, we report the performance of mosaic AOH identification using a low-pass (5~8-fold) WGS method (termed ‘CMA-seq’, an abbreviation for ‘Chromosome Analysis by Sequencing’) in fetal genetic diagnosis. Methods: Thirty AOH-negative, eleven constitutional AOH, and three mosaic AOH samples were collected as training data sets to develop the algorithm and evaluate the suitable thresholds for distinguishing mosaic AOH. Twenty-four new chromosomal aberrant cases, along with sixteen constitutional AOH samples, which were previously ascertained via the SNP-array-based method, were used as a validation data set to measure the performance in terms of sensitivity and specificity of this algorithm. Results: A new statistic, ‘D-value’, was implemented to identify and distinguish constitutional and mosaic AOH events. The reporting thresholds for constitutional and mosaic AOH were also established. In the validation set consisting of 24 new cases, seven constitutional AOH cases and 1 mosaic AOH case were successfully identified, indicating that the results were consistent with those of the SNP-array-based method. The results of all sixteen constitutional AOH validation samples also met the threshold requirements. Conclusions: In this study, we developed a new bioinformatic algorithm to accurately distinguish mosaic AOH from constitutional AOH by low-pass WGS. However, due to the small sample size of the training data set, the algorithm proposed in this manuscript still needs further refinements. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

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11 pages, 2257 KiB

Open AccessArticle

Implementation of Exome Sequencing in Prenatal Diagnostics: Chances and Challenges

by Ewa Janicki, Marjan De Rademaeker, Colombine Meunier, Nele Boeckx, Bettina Blaumeiser and Katrien Janssens

Diagnostics 2023, 13(5), 860; https://doi.org/10.3390/diagnostics13050860 - 23 Feb 2023

Cited by 6 | Viewed by 2533

Abstract

Whole exome sequencing (WES) has become part of the postnatal diagnostic work-up of both pediatric and adult patients with a range of disorders. In the last years, WES is slowly being implemented in the prenatal setting as well, although some hurdles remain, such [...] Read more.

Whole exome sequencing (WES) has become part of the postnatal diagnostic work-up of both pediatric and adult patients with a range of disorders. In the last years, WES is slowly being implemented in the prenatal setting as well, although some hurdles remain, such as quantity and quality of input material, minimizing turn-around times, and ensuring consistent interpretation and reporting of variants. We present the results of 1 year of prenatal WES in a single genetic center. Twenty-eight fetus-parent trios were analyzed, of which seven (25%) showed a pathogenic or likely pathogenic variant that explained the fetal phenotype. Autosomal recessive (4), de novo (2) and dominantly inherited (1) mutations were detected. Prenatal rapid WES allows for a timely decision-making in the current pregnancy, adequate counseling with the possibility of preimplantation or prenatal genetic testing in future pregnancies and screening of the extended family. With a diagnostic yield in selected cases of 25% and a turn-around time under 4 weeks, rapid WES shows promise for becoming part of pregnancy care in fetuses with ultrasound anomalies in whom chromosomal microarray did not uncover the cause. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

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19 pages, 4028 KiB

Open AccessArticle

Evaluation and Analysis of Absence of Homozygosity (AOH) Using Chromosome Analysis by Medium Coverage Whole Genome Sequencing (CMA-seq) in Prenatal Diagnosis

by Yan Lü, Yulin Jiang, Xiya Zhou, Na Hao, Guizhen Lü, Xiangxue Guo, Ruidong Guo, Wenjie Liu, Chenlu Xu, Jiazhen Chang, Mengmeng Li, Hanzhe Zhang, Jing Zhou, Wei (Victor) Zhang and Qingwei Qi

Diagnostics 2023, 13(3), 560; https://doi.org/10.3390/diagnostics13030560 - 2 Feb 2023

Cited by 2 | Viewed by 2925

Abstract

Objective: Absence of homozygosity (AOH) is a genetic characteristic known to cause human diseases mainly through autosomal recessive or imprinting mechanisms. The importance and necessity of accurate AOH detection has become more clinically significant in recent years. However, it remains a challenging task [...] Read more.

Objective: Absence of homozygosity (AOH) is a genetic characteristic known to cause human diseases mainly through autosomal recessive or imprinting mechanisms. The importance and necessity of accurate AOH detection has become more clinically significant in recent years. However, it remains a challenging task for sequencing-based methods thus far. Methods: In this study, we developed and optimized a new bioinformatic algorithm based on the assessment of minimum sequencing coverage, optimal bin size, the Z-score threshold of four types of allele count and the frequency for accurate genotyping using 28 AOH negative samples, and redefined the AOH detection cutoff value. We showed the performance of chromosome analysis by five-fold coverage whole genome sequencing (CMA-seq) for AOH identification in 27 typical prenatal/postnatal AOH positive samples, which were previously confirmed by chromosomal microarray analysis with single nucleotide polymorphism array (CMA/SNP array). Results: The blinded study indicated that for all three forms of AOH, including whole genomic AOH, single chromosomal AOH and segmental AOH, and all kinds of sample types, including chorionic villus sampling, amniotic fluid, cord blood, peripheral blood and abortive tissue, CMA-seq showed equivalent detection power to that of routine CMA/SNP arrays (750K). The subtle difference between the two methods is that CMA-seq is prone to detect small inconsecutive AOHs, while CMA/SNP array reports it as a whole. Conclusion: Based on our newly developed bioinformatic algorithm, it is feasible to detect clinically significant AOH using CMA-seq in prenatal diagnosis. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

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12 pages, 276 KiB

Open AccessArticle

Outcome of Fetal Dysrhythmias with and without Extracardiac Anomalies

by Stephanie Springer, Eva Karner, Elisabeth Seidl-Mlczoch, Guelen Yerlikaya-Schatten, Petra Pateisky and Barbara Ulm

Diagnostics 2023, 13(3), 489; https://doi.org/10.3390/diagnostics13030489 - 29 Jan 2023

Cited by 1 | Viewed by 1741

Abstract

Fetal dysrhythmias are common abnormalities, which can be categorized into three types: rhythm irregularities, tachyarrhythmias, and bradyarrhythmias. Fetal arrhythmias, especially in high-risk pregnancies, require special monitoring and treatment. The aim of this study was to assess the stillbirth and early and late neonatal [...] Read more.

Fetal dysrhythmias are common abnormalities, which can be categorized into three types: rhythm irregularities, tachyarrhythmias, and bradyarrhythmias. Fetal arrhythmias, especially in high-risk pregnancies, require special monitoring and treatment. The aim of this study was to assess the stillbirth and early and late neonatal mortality rates for pregnancies complicated by fetal dysrhythmias from one single tertiary referral center from 2000 to 2022. Of the 1018 fetuses with congenital heart disease, 157 (15.42%) were evaluated in this analysis. Seventy-four (46.7%) fetuses had bradyarrhythmias, 51 (32.5%) tachyarrhythmias, and 32 (20.4%) had rhythm irregularities. Additional structural heart defects were detected in 40 (25.3%) fetuses and extracardiac anomalies in 29 (18.4%) fetuses. Thirteen (8.2%) families opted for termination of the pregnancy. Eleven (7.6%), out of 144 continued pregnancies ended in spontaneous intrauterine fetal death (IUFD). Neonatal death was observed in nine cases (5.7%), whereas three (1.9%) died within the first 7 days of life. Although most intrauterine fetal deaths occurred in pregnancies with fetal bradyarrhythmia, neonatal death was observed more often in fetuses with tachyarrhythmia (8.5%). The presence of extracardiac anomalies, congenital heart disease (CHD), and Ro-antibodies are predictive factors for the occurrence of IUFD. Rhythm irregularities without any other risk factor do not present higher risks of adverse perinatal outcome. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

9 pages, 954 KiB

Open AccessArticle

Maternal and Neonatal Outcomes of Elective Induction of Labor at 39 or More Weeks: A Prospective, Observational Study

by Soobin Lee, Dong Hyun Cha, Cho Won Park and Eui Hyeok Kim

Diagnostics 2023, 13(1), 38; https://doi.org/10.3390/diagnostics13010038 - 23 Dec 2022

Cited by 1 | Viewed by 2735

Abstract

The purpose of our study is to compare the maternal and neonatal outcomes of induction of labor (IOL) versus expectant management at 39 weeks of gestation. We conducted a single-centered, prospective, observational study of nulliparous singleton women at 39 weeks or more. We [...] Read more.

The purpose of our study is to compare the maternal and neonatal outcomes of induction of labor (IOL) versus expectant management at 39 weeks of gestation. We conducted a single-centered, prospective, observational study of nulliparous singleton women at 39 weeks or more. We compared the maternal and perinatal outcomes. Of 408 nulliparous women, 132 women were IOL group and 276 women were expectant management group. IOL and expectant group had similar cesarean delivery rate (18.2% vs. 15.9%, p = 0.570). The delivery time from admission was longer in IOL group (834 ± 527 vs. 717 ± 469 min, p = 0.040). The IOL group was less likely to have Apgar score at 5 min < 7 than in expectant group (0.8% vs. 5.4%, p = 0.023). Multivariate analysis showed that IOL at 39 weeks was not an independent risk factor for cesarean delivery (relative risk 0.64, 95% confidence interval: 0.28–1.45, p = 0.280). Maternal and neonatal adverse outcomes, including cesarean delivery rate, were similar to women in IOL at 39 weeks of gestation compared to expectant management in nulliparous women. IOL at 39 weeks of gestation could be recommended even when the indication of IOL is not definite. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

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15 pages, 654 KiB

Open AccessArticle

Maternal Copy Number Imbalances in Non-Invasive Prenatal Testing: Do They Matter?

by Michaela Hyblova, Andrej Gnip, Marcel Kucharik, Jaroslav Budis, Martina Sekelska and Gabriel Minarik

Diagnostics 2022, 12(12), 3056; https://doi.org/10.3390/diagnostics12123056 - 6 Dec 2022

Cited by 2 | Viewed by 2769

Abstract

Non-invasive prenatal testing (NIPT) has become a routine practice in screening for common aneuploidies of chromosomes 21, 18, and 13 and gonosomes X and Y in fetuses worldwide since 2015 and has even expanded to include smaller subchromosomal events. In fact, the fetal [...] Read more.

Non-invasive prenatal testing (NIPT) has become a routine practice in screening for common aneuploidies of chromosomes 21, 18, and 13 and gonosomes X and Y in fetuses worldwide since 2015 and has even expanded to include smaller subchromosomal events. In fact, the fetal fraction represents only a small proportion of cell-free DNA on a predominant background of maternal DNA. Unlike fetal findings that have to be confirmed using invasive testing, it has been well documented that NIPT provides information on maternal mosaicism, occult malignancies, and hidden health conditions due to copy number variations (CNVs) with diagnostic resolution. Although large duplications or deletions associated with certain medical conditions or syndromes are usually well recognized and easy to interpret, very little is known about small, relatively common copy number variations on the order of a few hundred kilobases and their potential impact on human health. We analyzed data from 6422 NIPT patient samples with a CNV detection resolution of 200 kb for the maternal genome and identified 942 distinct CNVs; 328 occurred repeatedly. We defined them as multiple occurring variants (MOVs). We scrutinized the most common ones, compared them with frequencies in the gnomAD SVs v2.1, dbVar, and DGV population databases, and analyzed them with an emphasis on genomic content and potential association with specific phenotypes. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

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Graphical abstract

10 pages, 634 KiB

Open AccessArticle

HtrA1 in Gestational Diabetes Mellitus: A Possible Biomarker?

by Giovanni Tossetta, Sonia Fantone, Rosaria Gesuita, Gian Carlo Di Renzo, Arun Meyyazhagan, Chiara Tersigni, Giovanni Scambia, Nicoletta Di Simone and Daniela Marzioni

Diagnostics 2022, 12(11), 2705; https://doi.org/10.3390/diagnostics12112705 - 5 Nov 2022

Cited by 18 | Viewed by 1815

Abstract

Background: The high-temperature requirement A 1 (HtrA1) is a multidomain secretory protein with serine-protease activity, expressed in many tissues, including placenta, where its expression is higher in the first trimester, suggesting an association of this serine protease in early phases of human placenta [...] Read more.

Background: The high-temperature requirement A 1 (HtrA1) is a multidomain secretory protein with serine-protease activity, expressed in many tissues, including placenta, where its expression is higher in the first trimester, suggesting an association of this serine protease in early phases of human placenta development. In this study, we evaluated maternal serum HtrA1 levels in the first and third trimester of gestation. In particular, we evaluated a possible role of HtrA1 as an early marker of gestational diabetes mellitus (GDM) in the first trimester of gestation. Methods: We evaluated HtrA1 serum levels in the third trimester (36–40 weeks) in normal pregnancies (n = 20) and GDM pregnancies (n = 20) by using ELISA analysis. Secondly, we performed the same analysis by using the first trimester sera (10–12 weeks) of healthy pregnant women that will develop a normal pregnancy (n = 210) or GDM (n = 28) during pregnancy. Results: We found that HtrA1 serum levels in the third trimester were higher in pregnancies complicated by GDM. Interestingly, higher HtrA1 serum levels were also found in the first trimester in women developing GDM later during the second–third trimester. No significant differences in terms of maternal age and gestational age were found between cases and controls. Women with GDM shown significantly higher pre-pregnancy BMI values compared to controls. Moreover, the probability of GDM occurrence significantly increased with increasing HtrA1 levels and BMI values. The ROC curve showed a good accuracy in predicting GDM, with an AUC of 0.74 (95%CI: 0.64–0.92). Conclusions: These results suggest an important role of HtrA1 as an early predictive marker of GDM in the first trimester of gestation, showing a significative clinical relevance for prevention of this disease. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

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Review

Jump to: Research, Other

18 pages, 2500 KiB

Open AccessReview

A Novel Paradigm for Non-Invasive Prenatal Genetic Screening: Trophoblast Retrieval and Isolation from the Cervix (TRIC)

by Kirim Hong, Hee Jin Park, Hee Yeon Jang, Sung Han Shim, Yoon Jang, Soo Hyun Kim and Dong Hyun Cha

Diagnostics 2023, 13(15), 2532; https://doi.org/10.3390/diagnostics13152532 - 30 Jul 2023

Viewed by 2191

Abstract

As the prevalence of pregnancies with advanced maternal age increases, the risk of fetal chromosomal abnormalities is on the rise. Therefore, prenatal genetic screening and diagnosis have become essential elements in contemporary obstetrical care. Trophoblast retrieval and isolation from the cervix (TRIC) is [...] Read more.

As the prevalence of pregnancies with advanced maternal age increases, the risk of fetal chromosomal abnormalities is on the rise. Therefore, prenatal genetic screening and diagnosis have become essential elements in contemporary obstetrical care. Trophoblast retrieval and isolation from the cervix (TRIC) is a non-invasive procedure that can be utilized for prenatal genetic diagnosis. The method involves the isolation of fetal cells (extravillous trophoblasts) by transcervical sampling; along with its non-invasiveness, TRIC exhibits many other advantages such as its usefulness in early pregnancy at 5 weeks of gestation, and no interference by various fetal and maternal factors. Moreover, the trophoblast yields from TRIC can provide valuable information about obstetrical complications related to abnormal placentation even before clinical symptoms arise. The standardization of this clinical tool is still under investigation, and the upcoming advancements in TRIC are expected to meet the increasing need for a safe and accurate option for prenatal diagnosis. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

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11 pages, 559 KiB

Open AccessReview

Non-Invasive Prenatal Testing in Germany

by Thomas Liehr, Tigran Harutyunyan, Heather Williams and Anja Weise

Diagnostics 2022, 12(11), 2816; https://doi.org/10.3390/diagnostics12112816 - 16 Nov 2022

Cited by 9 | Viewed by 4284

Abstract

In the short 10 years following the introduction of non-invasive prenatal testing (NIPT), it has been adapted in many countries around the world as a standard screening test. In this review, this development was analyzed with a special focus on Germany. As a [...] Read more.

In the short 10 years following the introduction of non-invasive prenatal testing (NIPT), it has been adapted in many countries around the world as a standard screening test. In this review, this development was analyzed with a special focus on Germany. As a result, it can be stated that all known advantages of NIPT apart from “compensating for having no access to centers offering invasive diagnostics” are valid for Germany. In addition, following a review of the international literature, all documented issues with NIPT are also observed in Germany. However, the German Gene Diagnostics Act (GenDG) addresses a number of these issues, for example, the regulations by GenDG hamper induced abortions, based exclusively on an abnormal NIPT result. At the same time, GenDG has created new problems, as a possible collusion between the “right not to know with regard to parts of the examination result” may occur, or that the sex of the fetus must not be reported to the pregnant woman before the 12th week of gestation. Main conclusions drawn are that appropriate training and the continuing education of the physicians providing NIPT-related counseling are needed, as well as the provision of balanced and comprehensive information for the pregnant woman or the couple that is imperative. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

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Other

Jump to: Research, Review

10 pages, 2349 KiB

Open AccessCase Report

Prenatal Diagnosis of Uniparental Disomy in Cases of Rare Autosomal Trisomies Detected Using Noninvasive Prenatal Test: A Case of Prader–Willi Syndrome

by Da Kyung Hong, Ji Eun Park, Kyung Min Kang, Sung Han Shim, So Hyun Shim, You Jung Han, Hee Young Cho and Dong Hyun Cha

Diagnostics 2023, 13(4), 580; https://doi.org/10.3390/diagnostics13040580 - 4 Feb 2023

Viewed by 2855

Abstract

Rare autosomal trisomies (RATs) other than common aneuploidies can be detected using noninvasive prenatal testing (NIPT). However, conventional karyotyping is insufficient for evaluating diploid fetuses with uniparental disomy (UPD) due to trisomy rescue. Using the diagnostic process for Prader–Willi syndrome (PWS), we aim [...] Read more.

Rare autosomal trisomies (RATs) other than common aneuploidies can be detected using noninvasive prenatal testing (NIPT). However, conventional karyotyping is insufficient for evaluating diploid fetuses with uniparental disomy (UPD) due to trisomy rescue. Using the diagnostic process for Prader–Willi syndrome (PWS), we aim to describe the need for additional prenatal diagnostic testing for confirming UPD in fetuses diagnosed with RATs via NIPT and its clinical implications. NIPT was performed using the massively parallel sequencing (MPS) method, and all pregnant women with RATs underwent amniocentesis. After confirming the normal karyotype, short tandem repeat (STR) analysis, methylation-specific PCR (MS-PCR), and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were performed to detect UPD. Overall, six cases were diagnosed with RATs. There was a suspicion of trisomies of chromosomes 7, 8, and 15 in two cases each. However, these cases were confirmed to have a normal karyotype using amniocentesis. In one of six cases, PWS caused by maternal UPD 15 was diagnosed using MS-PCR and MS-MLPA. We propose that in cases where RAT is detected by NIPT, UPD should be considered following trisomy rescue. Even if amniocentesis confirms a normal karyotype, UPD testing (such as MS-PCR and MS-MLPA) should be recommended for accurate assessment, as an accurate diagnosis can lead to appropriate genetic counseling and improved overall pregnancy management. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

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11 pages, 471 KiB

Open AccessSystematic Review

The Proper Diagnosis of Thrombophilic Status in Preventing Fetal Growth Restriction

by Bianca-Margareta Mihai, Teodor Salmen, Ana-Maria Cioca and Roxana-Elena Bohîlțea

Diagnostics 2023, 13(3), 512; https://doi.org/10.3390/diagnostics13030512 - 31 Jan 2023

Cited by 2 | Viewed by 2097

Abstract

Fetal growth restriction is an important part of monitoring a pregnancy. Because guidelines or diagnostic criteria for either minor or major thrombophilia are scarce, this systematic review aims to summarize the present knowledge in the field. We performed the CRD42022376006 protocol in Prospero [...] Read more.

Fetal growth restriction is an important part of monitoring a pregnancy. Because guidelines or diagnostic criteria for either minor or major thrombophilia are scarce, this systematic review aims to summarize the present knowledge in the field. We performed the CRD42022376006 protocol in Prospero with a systematic literature search in PubMed and Web of Science databases and included original full-text articles (randomized control trials and clinical trials) from the last 10 years, published in English, and with the “thrombophilia AND (pregnancy OR diagnostic criteria) AND fetal growth restriction” criteria. After two researchers extracted the articles of interest, they were assessed using the Newcastle–Ottawa Scale and eight articles were included. The elements from the thrombophilia diagnostic predict IUGR, factor V Leiden mutation, MTHFR C667T mutation, protein S deficiency, antithrombin deficiency, factor VII polymorphism, and antiphospholipid antibodies, while the association of protein C, PAI-1 and certain combinations of mutations are still under debate and require the collection of more data. The present systematic review provides an extensive picture of the actual knowledge about thrombophilia diagnosis and its links with pregnancy complications, such as intrauterine growth restriction, despite its limitation in the inclusion of other actually debated disorders such as PAI-1 mutation, protein C deficiency and other thrombophilia types. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

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14 pages, 1100 KiB

Open AccessSystematic Review

Echogenic Content in the Fetal Gallbladder: Systematic Review of Ultrasound Features and Clinical Outcome

by Dan Boitor-Borza, Ioana Cristina Rotar, Adelina Staicu, Roxana Constantin and Daniel Muresan

Diagnostics 2023, 13(2), 230; https://doi.org/10.3390/diagnostics13020230 - 8 Jan 2023

Cited by 1 | Viewed by 4479

Abstract

It is rare to detect echogenic content in the fetal gallbladder. The etiology, natural course, and prognosis of this condition remain unclear. In addition to providing a systematic review of this topic, we suggest a plan for patient follow-up. From a total of [...] Read more.

It is rare to detect echogenic content in the fetal gallbladder. The etiology, natural course, and prognosis of this condition remain unclear. In addition to providing a systematic review of this topic, we suggest a plan for patient follow-up. From a total of 100 database entries identified in PubMed, EMBASE, and ICTRP reviews, we selected 34 studies in which we investigated the ultrasound features and outcome of this condition. There were 226 fetuses with gallbladder echogenic content identified. Seventy-two fetuses were found to have biliary sludge; thirty cases had a single hyperechogenic focus, and one hundred fetuses had multiple foci in the gallbladder. There were 16 cases of distal shadowing, 37 fetuses with comet tail and twinkling, and 26 cases with no acoustic artifacts. Nine cases of spontaneous resolution before birth have been documented; nine fetuses exhibited no echogenic content at birth, and 138 cases of resolution of echogenic content within the first year of life have been described. Typically, the condition resolves spontaneously during the postnatal period. After adequately reassuring the parents, the patients should be monitored for spontaneous resolution; medical or surgical intervention is not indicated. Asymptomatic patients can be managed with a wait-and-see strategy. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

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13 pages, 1160 KiB

Open AccessSystematic Review

Accuracy of Non-Invasive Prenatal Testing for Duchenne Muscular Dystrophy in Families at Risk: A Systematic Review

by Luca Zaninović, Marko Bašković, Davor Ježek and Ana Katušić Bojanac

Diagnostics 2023, 13(2), 183; https://doi.org/10.3390/diagnostics13020183 - 4 Jan 2023

Cited by 1 | Viewed by 3201

Abstract

Background: Methodological advancements, such as relative haplotype and relative mutation dosage analyses, have enabled non-invasive prenatal diagnosis of autosomal recessive and X-linked diseases. Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by progressive proximal muscular dystrophy and a high mortality rate [...] Read more.

Background: Methodological advancements, such as relative haplotype and relative mutation dosage analyses, have enabled non-invasive prenatal diagnosis of autosomal recessive and X-linked diseases. Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by progressive proximal muscular dystrophy and a high mortality rate before the age of twenty. We aimed to systematically present obtainable data regarding a non-invasive prenatal diagnosis of DMD and provide a comprehensive resume on the topic. The emphasis was given to the comparison of different available protocols and molecular methods used for fetal inheritance deduction, as well as their correlation with prognostic accuracy. Methods: We searched the Scopus and PubMed databases on 11 November 2022 and included articles reporting a non-invasive prenatal diagnosis of DMD in families at risk using relative dosage analysis methods. Results: Of the 342 articles identified, 7 met the criteria. The reported accuracy of NIPT for DMD was 100% in all of the studies except one, which demonstrated an accuracy of 86.67%. The combined accuracy for studies applying indirect RHDO, direct RHDO, and RMD approaches were 94.74%, 100%, and 100%, respectively. Confirmatory results by invasive testing were available in all the cases. Regardless of the technological complexity and low prevalence of the disease that reduces the opportunity for systematic research, the presented work demonstrates substantial accuracy of NIPT for DMD. Conclusions: Attempts for its implementation into everyday clinical practice raise many ethical and social concerns. It is essential to provide detailed guidelines and arrange genetic counseling in order to ensure the proper indications for testing and obtain informed parental consent. Full article

(This article belongs to the Special Issue Prenatal Diagnosis: Current Trends and Future Directions)

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