Genetic Testing Methods Research Articles

Retinal diseases constitute a clinically and genetically heterogeneous group of disorders characterized by progressive dysfunction or degeneration of the neural retina and/or retinal pigment epithelium. In recent years, molecular genetic testing methods have become indispensable tools for the diagnosis, subclassification, and management of these conditions. Techniques based on next-generation sequencing (NGS), including targeted gene panels, whole-exome sequencing (WES), and whole-genome sequencing (WGS), have significantly expanded our understanding of pathogenic variants and facilitated the discovery of novel gene-disease associations. In addition to their diagnostic utility, these tests play a critical role in genetic counseling, carrier detection, assessment of therapeutic eligibility, and recruitment into clinical trials. Despite their growing clinical relevance, genetic tests raise complex ethical challenges. Predictive and prenatal testing—especially in disorders for which no effective treatment currently exists—pose dilemmas related to autonomy, confidentiality, informed consent, and distributive justice. Furthermore, disparities in access to emerging gene-based therapies, the application of testing in minors and unborn individuals, concerns surrounding the privacy of genetic data, and the obligation to recontact patients when new clinically significant information becomes available represent key areas of ethical concern. These issues underscore the need for well-defined policies and multidisciplinary approaches to ensure ethically responsible integration of genetic testing into ophthalmic care.

Ballast water plays a crucial role in maintaining ship stability, yet it remains a major pathway for the spread of invasive marine species. Regulations introduced by the International Maritime Organization (IMO) now require vessels to treat ballast water before discharge, prompting widespread retrofitting of treatment systems. A broad review of research highlights the diverse adoption of prominent technologies, such as electrolysis and ozonation, alongside significant attention on ultraviolet (UV) treatment methods. The overall trend in ballast water management emphasizes greater system stability, lower operational costs, and improved ease of operation and maintenance over a single dominant technology. Publication trends show growing international collaboration and increasing focus on regulatory compliance, cost analysis, and environmental impact. Evaluations across various studies point to seven key aspects in retrofit planning, including system selection, spatial layout, compliance with international standards, and integration of advanced modeling tools. While many retrofit projects prioritize efficiency and cost, fewer have addressed long-term monitoring or biological risk mitigation. Differences in regulatory frameworks across countries create compliance gaps, while newer risks, such as persistent microorganisms and radioactive discharge, remain difficult to control with current systems. Emerging tools, including real-time monitoring devices and genetic testing methods, offer promise for improving system performance and post-installation validation. Retrofit planning increasingly incorporates digital engineering, helping to reduce installation time and minimize costs. Global cooperation remains essential, especially when managing compliance in international waters. Addressing both known and emerging challenges requires a combination of strong technical planning, legal harmonization, and environmental awareness. A more integrated approach will support sustainable marine operations and help safeguard ocean ecosystems from the long-term effects of untreated ballast water. ------------------------------------------------------------------------------Cite this article: Sari, W. R., Gunawan, & Muzhoffar, D. A. F. (2026). Trend for ballast water treatment system retrofits. Maritime Technology and Research, 8(1), 281429. https://doi.org/10.33175/mtr.2026.281429 ------------------------------------------------------------------------------ Highlights The study uses an integrated, three-stage framework comprising descriptive, bibliometric, and systematic analysis to comprehensively assess the landscape of BWTS retrofit research. This multi-faceted approach goes beyond a simple summary to generate new insights into the interplay of technological, regulatory, and operational factors. Ultraviolet (UV) treatment is the most dominant and cost-effective BWTS technology, with 72 publications in the abstract, reflecting its prominence in research. However, UV efficiency is highly dependent on water quality, and studies found system failures in waters with high Total Suspended Solids (TSS). In addition to UV, electrolysis and ozonation are also widely adopted, with electrolysis showing growing research interest, as evidenced by 74 publications by abstract. Seven key stages for retrofitting BWTS are defined, including assessment and planning, space selection, regulatory compliance, BWTS method selection, engineering drawing and 3D modeling, installation planning, and commissioning and integration. Global research trends show that the United States and China are the leaders in BWTS research. China has the highest number of documents with 61 and citations with 800. The United States, while having fewer documents, shows a stronger collaboration link strength about 117 compared to China's about 67, indicating a more prominent role in shaping research directions through its collaborative network. The use of advanced tools like 3D scanning and CAD modeling is increasing to improve retrofit efficiency and reduce costs. These methodologies have been shown to cut project time by approximately 25 % and total costs by about 15 %. Furthermore, frameworks like fuzzy logic and life-cycle costing are used to help ship operators make optimal decisions based on various criteria, including cost and operational constraints.

Genome-wide single nucleotide polymorphism (SNP) genotyping using microarrays and karyomapping (parental haplotyping) is a universal linkage-based method for preimplantation genetic testing of monogenic disease (PGT-M) and identification of chromosome aneuploidies, including meiotic trisomies, monosomies and deletions. Following IVF, embryos are biopsied at the blastocyst stage and several trophectoderm cells removed. Both parents, a close relative of known disease status and the biopsy samples are genotyped and parental haplotypes analysed. Here we extended the method by combining parental haplotyping with parental intensity ratio analysis. This enables identification of meiotic and mitotic, whole and segmental aneuploidies at high resolution. In 342 cycles of PGT-M in couples with a mean maternal age of 32.9 ± 4.2 (SD), 37% (471/1270) of the biopsy samples were identified as aneuploid with an almost equal number of meiotic and mitotic aneuploidies. Meiotic aneuploidies were predominantly whole chromosome aneuploidies of maternal origin and increased with maternal age. Mitotic aneuploidies (with normal biparental haplotype patterns) were mainly segmental imbalances. For PGT of aneuploidy (PGT-A) in infertile couples, identifying meiotic aneuploidies, which are almost all non-viable, provides a valuable option to minimise the discard of embryos with only mitotic aneuploidies of unknown clinical outcome.

Abstract Background and Aims The early clinical signs of Gitelman syndrome (GS) are often non-specific, making diagnosis primarily dependent on genetic testing methods. Identifying potential biomarkers linked to GS is crucial for the early diagnosis and treatment of the condition. This study aims to examine the changes in serum metabolite levels in GS patients and to validate their potential as diagnostic biomarkers. Method This study analyzed 5 GS patients from Yunnan's Yi community and 7 controls from the same area. Serum samples were collected and analyzed using UHPLC-Q-TOF for untargeted metabolomics analysis. PCA and OPLS-DA were used for statistical evaluation, and metabolites' pathways were explored with HMDB and LMSD. Differential metabolites were identified using heat map significance (P < 0.05), fold change (FC > 1.5 or FC < 2/3), and VIP > 1 criteria. ROC curves were applied to evaluate these metabolites as potential biomarkers. Results Serum metabolomics analysis revealed a strong association between differential metabolic pathways and lipid metabolism in patients with GS. This study identified 27 differentially expressed metabolites through screening and enrichment processes. A pathway enrichment analysis was conducted on these metabolites, identifying 10 metabolic pathways related to GS. The results indicated that the most significant metabolic pathways included glycerophospholipid metabolism, linoleic acid metabolism, and the biosynthetic metabolism of pantothenic acid and coenzyme A. Hexanoylglycine (HG) and PE (P-18:0/19:1) were primarily noted among the differentially expressed metabolites. Additionally, we measured serum total cholesterol (TC) levels and body mass index (BMI) in patients with GS. The findings showed that GS patients had significantly lower serum TC levels and BMI values compared to the healthy control group. This suggests that their lipid metabolism function may be impaired, aligning with our untargeted metabolomics analysis results. Conclusion This study highlights the potential significance of lipid metabolism in the development of GS. HG and PE (P-18:0/19:1) could be novel biomarkers for diagnosing GS.

Abstract Background and Aims Autosomal dominant tubulointerstitial kidney disease (ADTKD) encompasses a group of hereditary kidney disorders characterized by tubulointerstitial fibrosis. These conditions typically follow an autosomal dominant inheritance pattern and are subclassified based on their genetic cause when identified. Pathogenic variants in UMOD, MUC1, REN, HNF1B, and SEC61A1 have been implicated in ADTKD pathogenesis. Advances in molecular diagnostics have improved genetic identification, though the true prevalence is likely underestimated. We present a cohort of ADTKD patients identified in the Nephrogenetics’ Clinic of our department between 2010 and 2024. Method Patients with chronic kidney disease (CKD) of unknown cause and undefined phenotype, or those exhibiting a renal phenotype suggestive of chronic interstitial nephritis, particularly with a family history of similar CKD, were referred to the Nephrogenetics’ Clinic for ADTKD investigation. Genetic testing methods evolved over time: Before 2015, Sanger sequencing was used. Since 2015, a stepwise genetic approach was used: (1) next-generation sequencing (NGS) for UMOD, REN, HNF1B, and SEC61A1; (2) if negative, targeted analysis for the insertion of a single cytosine in the variable-number tandem repeat (VNTR) sequence of MUC1; (3) if still negative, multiplex ligation-dependent probe amplification (MLPA) was performed to detect HNF1B deletions (P241-D2 kit, MRC-Holland). For patients with CKD and undefined phenotype, broader NGS panels for CKD were applied. Negative results underwent periodic re-evaluation, including deeper phenotyping when possible, and re-analysis using expanded gene panels, whole-exome sequencing (WES), or additional methods in reference laboratories. Pre-test genetic counseling was conducted by a nephrologist, while post-test counseling was performed jointly by a nephrologist and a geneticist, particularly for family screening and segregation studies. Results Among 35 families studied, a confirmed genetic diagnosis was obtained in 15 (43%), identifying 42 patients with ADTKD. The implicated variants were: MUC1: 5 families (18 patients); UMOD: 4 families (11 patients, all diagnosed via Sanger sequencing); HNF1B: 5 families (12 patients); REN: 1 patient with biallelic REN mutations (heterozygous). Four families presented with an undefined phenotype: two families underwent CKD panel testing due to young age at onset; two families had a cystic kidney phenotype and were tested using a cystic kidney disease panel. Notably, all these families harbored pathogenic or likely pathogenic HNF1B variants. One family underwent additional PacBio sequencing for MUC1 at a reference laboratory, leading to the identification of the dup60A variant in MUC1. Re-analysis of negative results led to the identification of pathogenic variants in two additional families: COL4A3 (heterozygous) in 1 family (2 patients); SDCCAG8 (homozygous) in 1 family (2 patients). Likely pathogenic variants were identified in: PAX2 in 1 family (3 patients); PKD1 in 1 family (3 patients); COL4A5 in 1 family (3 patients). Studies are ongoing in two families, while the remaining negative cases will undergo re-evaluation. Additionally, segregation studies are in progress for three families to assess the pathogenicity of variants in: UMOD (1 family, at least 2 patients); HNF1B (1 family, 2 patients); a family with CKD (3 patients) where the index patient carries VUS in both HNF1B and UMOD. Conclusion A genetic diagnosis of ADTKD was established in 43% of the families studied, and genetic CKD was confirmed in 57% of the families. MUC1 and UMOD were the most prevalent genes associated with ADTKD, though a significant number of cases involved HNF1B (mostly CNVs). Re-analysis of initially negative results increased the diagnostic yield for ADTKD and genetic CKD with an ADTKD-like phenotype. These findings suggest that broader gene panels as a first-line approach may enhance diagnostic accuracy. Additionally, the limitations of NGS and WES in detecting MUC1 and HNF1B variants underscore the importance of collaboration with specialized reference laboratories for ADTKD diagnosis.

ObjectiveAdenomatous polyposis syndrome (APS) is a rare hereditary disease characterized by the development of multiple (more than 20) adenomas of the colon with a high-risk of malignant transformation without surgical treatment. The most aggressive form of APS, with >100 polyps before the age of 45 years, is mostly caused by germline pathogenic variants in the APC gene but patients with germline variants in the MUTYH and, very rarely, in the SMAD4 and BMPR1A genes were also reported. Routine molecular testing methods, such as Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA) or multigene NGS panels, may fail to detect pathogenic variants in non-coding regions.Patients and methodsDNA from blood samples of 10 patients (with age of APS manifestation between 15 and 45 years) with over 100 adenomatous colonic polyps identified by endoscopic examination was subjected to whole genome sequencing (WGS). Prior genetic testing did not detect any germline pathogenic variants in the APC and MUTYH coding exons in these patients.ResultsPathogenic and likely pathogenic germline variants in non-coding regions of genes were identified in 3 patients. Two unrelated patients had the same c.-190G>A (rs879253785) in the 1B promoter of the APC gene (NM_001127511.3), while the third patient had a c.-152-2A>G variant in the BMPR1A gene (NM_004329.3). Using standard NGS panels or whole exome sequencing (WES) would not have detected these variants.ConclusionOur results demonstrate that WGS is a useful genetic testing method for young patients with over 100 adenomatous colonic polyps, when routine DNA diagnostic methods fail to establish the genetic cause of the disease.

Robin sequence (RS) is a congenital condition characterized by micrognathia, glossoptosis, and upper airway obstruction, often occurring with cleft palate and syndromic conditions. The genetic basis of RS is heterogeneous, including monogenic variants and chromosomal rearrangements. This systematic review synthesizes the current genetic landscape of RS, analyzing data from 107 studies that employed various genetic testing methods, including chromosomal microarray (CMA), targeted sequencing, and whole exome sequencing (WES). A distinction is made between genetic variants identified in isolated versus non-isolated RS. Pathogenic variants in genes as SOX9, SNRPB, SATB2, TGDS, RBM10, COL11A1, and COL2A1 are frequently identified, many of which are linked to non-isolated RS. The most common chromosomal aberrations are deletions of 22q11.2 and 18q. Up-to-date genetic testing is essential to enable accurate diagnosis and personalized clinical care. With the growing use of whole genome sequencing (WGS) in clinical practice, the need for phenotype-driven interpretation tools is increasing. Some platforms can prioritize gene relevance based on Human Phenotype Ontology (HPO) terms. Documenting both known and novel RS-associated genes is therefore crucial to fully realize the diagnostic potential of WGS and support evidence-based clinical decision-making.

Diagnosis and selection of effective therapy of soft tissue sarcomas (STS) are complicated by low incidence and significant histological variability of these tumors. Development of molecular and genetic testing methods is aimed at improving differential diagnosis of different types of STS and identification of genetic abnormalities which can potentially serve as targets for therapy. Development of effective treatment methods requires adequate preclinical models capable of recreating biological features of the tumors. The article presents molecular and genetic testing methods for STS diagnosis and therapy, advances in in vitro STS models, problems with their use in preclinical studies, as well as possibilities of using primary cell cultures for personalized treatment.

Genetics and pathobiology were addressed at the 7th World Symposium on Pulmonary Hypertension in Task Forces 2 and 3. The Genetics Task Force also focused on precision medicine approaches, and the Pathobiology working group concentrated heavily on new omics technologies. Therefore, the following not only summarises the current state of knowledge on genetics, genetic testing methods, and molecular pathophysiological changes, but also places it in context and critically discusses it. In addition, the importance of national and international biobanks and cohorts, as well as the active involvement of patients and families, is emphasized.

Uncertainties, risks, or hope? Managing embryos in a multidisciplinary team of PGT.

BackgroundShort-read genome sequencing (GS) is among the most comprehensive genetic testing methods available, capable of detecting single-nucleotide variants, copy-number variants, mitochondrial variants, repeat expansions, and structural variants in a single assay. Despite its technical advantages, the full clinical utility of GS in real-world diagnostic settings remains to be fully established.MethodsThis study systematically compared singleton GS (sGS), trio GS (tGS), and exome sequencing-based standard-of-care (SoC) genetic testing in 416 patients with rare diseases in a blinded, prospective study. Three independent teams with divergent baseline expertise evaluated the diagnostic yield of GS as a unifying first-tier test and directly compared its variant detection capabilities, learning curve, and clinical feasibility. The SoC team had extensive prior experience in exome-based diagnostics, while the sGS and tGS teams were newly trained in GS interpretation. Diagnostic yield was assessed through both prospective and retrospective analyses.ResultsIn our prospective analysis, tGS achieved the highest diagnostic yield for likely pathogenic/pathogenic variants at 36.1% in the newly trained team, surpassing the experienced SoC team at 35.1% and the newly trained sGS team at 28.8%. To evaluate which variants could technically be identified and account for differences in team experience, we conducted a retrospective analysis, achieving diagnostic yields of 36.7% for SoC, 39.1% for sGS, and 40.0% for tGS. The superior yield of GS was attributed to its ability to detect deep intronic, non-coding, and small copy-number variants missed by SoC. Notably, tGS identified three de novo variants classified as likely pathogenic based on recent GeneMatcher collaborations and newly published gene-disease association studies.ConclusionsOur findings demonstrate that GS, particularly tGS, outperforms SoC in diagnosing rare diseases, with sGS providing a more cost-effective alternative. These results suggest that GS should be considered a first-tier genetic test, offering an efficient, single-step approach to reduce the diagnostic odyssey for patients with rare diseases. The trio approach proved especially valuable for less experienced teams, as inheritance data facilitated variant interpretation and maintained high diagnostic yield, while experienced teams achieved comparable results with singleton analysis alone.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13073-025-01516-7.

Acute ischemic stroke (AIS) remains a leading cause of mortality and long-term disability globally, with survivors at high risk of recurrent stroke, cardiovascular events, and post-stroke dementia. Statins, while widely used for their lipid-lowering effects, also possess pleiotropic properties, including anti-inflammatory, endothelial-stabilizing, and neuroprotective actions, which may offer added benefit in AIS management. This article synthesizes emerging evidence on statins' dual mechanisms of action and evaluates their role in reducing recurrence, improving survival, and mitigating cognitive decline. Key challenges limiting the full therapeutic potential of statins include interindividual variability in response and pharmacogenomic and biomarker-related resistance, inconsistencies across clinical guidelines, and limited central nervous system bioavailability. Innovations such as pharmacogenomic-guided therapy, pleiotropy-linked biomarkers, and advanced drug delivery systems (e.g., nanoparticle and intranasal formulations) may help overcome these barriers. Combination strategies with agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors or sodium-glucose cotransporter 2 (SGLT2) inhibitors, and targeted interventions against neuroinflammatory resistance, show promise in enhancing treatment efficacy. In doing so, we propose a shift from conventional statin use to a precision medicine paradigm that can better serve AIS survivors, especially those at risk of post-stroke dementia or those living in resource-constrained settings. While such innovations, for example, genetic testing and novel delivery methods, may not yet be feasible in all contexts, particularly low-resource environments, they represent long-term goals for equity-driven innovation. Equity in access to high-intensity statins and novel therapies remains a global priority, particularly in low- and middle-income countries. Future research should prioritize personalized, biomarker-driven approaches and inclusive clinical trials to optimize statin use across diverse AIS populations. By advancing these strategies, statins can evolve from cardiovascular agents into integral components of precision neurovascular medicine, improving long-term outcomes and quality of life for stroke survivors.

BackgroundPatients with neuromuscular diseases (NMD) have undergone considerable technological progress in terms of diagnosis and treatment over the past few years. Specifically, next-generation sequencing (NGS) has significantly expanded genetic diagnosis. Despite this, some patients remain undiagnosed and therefore without access to specific treatments. Analyses of epidemiology and diagnostic approaches in reference centers are required to determine effective strategies to improve diagnostic rates.MethodsWe studied the proportion of each NMD and associated investigations in the patient population of the Neuromuscular Reference Center (NMRC) of Liege, Belgium, in 2023. The investigation tools used included laboratory testing, muscle biopsy, muscle imaging, single-gene sequencing, targeted NGS panels, and whole-exome sequencing (WES).ResultsOf the 1084 patients who were regularly followed up, more than one-third had neuropathies (36.6%) that were divided equally between genetic and acquired causes. The second most common disorder was muscular dystrophies, which represented more than a quarter (27.5%). Third, 11.2% of the patients had motor neuron diseases. The other NMD (i.e., myopathies, ataxias, spastic paraplegias, and channelopathies) ranged from 2.1% to 6. %. A total of 13.7% of the patients had unconfirmed diagnoses, 31.5% had confirmed acquired disorders, and 54.9% had genetically confirmed disorders. Among the genetic diagnoses, 32.7% were obtained by NGS. The remaining 67.3% were determined using other genetic testing methods [i.e., array comparative genomic hybridization (aCGH), multiplex ligation-dependent probe amplification (MLPA), polymerase chain reaction (PCR), southern blotting (SB)].ConclusionMore than two-thirds of patients received a definitive diagnosis without the use of next-generation sequencing. Although innovative technologies such as whole genome sequencing and long-read sequencing are expected to eventually replace NGS panels and traditional methods (e.g., MLPA, PCR, aCGH), their current cost and the complexity of variant interpretation limit their widespread use in routine clinical practice. As a result, these older techniques remain relevant and valuable in current diagnostic workflow.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13023-025-03963-2.

Background: Inborn errors of immunity (IEI) are mainly genetically driven disorders that affect immune function and present with highly heterogeneous clinical manifestations, ranging from severe combined immunodeficiency (SCID) to adult-onset immune dysregulatory diseases. This clinical heterogeneity, coupled with limited awareness and the absence of a universal diagnostic test, makes early and accurate diagnosis challenging. Although genetic testing methods such as whole-exome and genome sequencing have improved detection, they are often expensive, complex, and require functional validation. Recently, artificial intelligence (AI) tools have emerged as promising for enhancing diagnostic accuracy and clinical decision-making for IEI. Methods: We conducted a systematic review of four major databases (PubMed, Scopus, Web of Science, and Embase) to identify peer-reviewed English-published studies focusing on the application of AI techniques in the diagnosis and treatment of IEI across pediatric and adult populations. Twenty-three retrospective/prospective studies and clinical trials were included. Results: AI methodologies demonstrated high diagnostic accuracy, improved detection of pathogenic mutations, and enhanced prediction of clinical outcomes. AI tools effectively integrated and analyzed electronic health records (EHRs), clinical, immunological, and genetic data, thereby accelerating the diagnostic process and supporting personalized treatment strategies. Conclusions: AI technologies show significant promise in the early detection and management of IEI by reducing diagnostic delays and healthcare costs. While offering substantial benefits, limitations such as data bias and methodological inconsistencies among studies must be addressed to ensure broader clinical applicability.

Evidence on the prevalence of HLA-B*58:01 genotyping and its association with allopurinol-induced severe cutaneous adverse reactions (SCARs) is lacking, especially in low-resource settings. We addressed these gaps by conducting comprehensive and race/ethnic origin-specific evaluations. We conducted a systematic search from inception to 31 December 2022 using databases (PubMed, Embase, and medRxiv), Google (for Vietnamese articles), and manual searching. We included original studies that investigated the association between HLA-B*58:01 genotyping and allopurinol-induced SCARs. We excluded studies on: (1) animals; (2) pharmacokinetics/pharmacodynamics; (3) genetic markers or genetic testing methods; (4) single group; and (5) cost-effectiveness of screening. Risk of bias was assessed using Newcastle-Ottawa Scale. We used random-effects model to report the summary estimates and 95% confidence interval (95% CI) in the meta-analysis. We included 13,719 patients from 24 case-control studies. The prevalences of HLA-B*58:01 genotyping (overall 5.8%; 95% CI 2.9% to 11.5%; I2 = 98%) varied by races (Asian [7.7%; 95% CI 3.4% to 16.8%; I2 = 98%] and White in Eastern/Western Europe [2.3%; 95% CI 1.2% to 4.3%; I2 = 86%]) and ethnic origins (East and Central Asia [5.5%; 95% CI 1.5% to 17.8%; I2 = 98%] and South and Southeast Asia [12.9%; 95% CI 9.5% to 17.3%; I2 = 79%]). HLA-B*58:01 genotyping was associated with substantially increasing risk of allopurinol-induced SCARs (odds ratio 117.6; 95% CI 70.3 to 196.8; I2 = 45%) regardless of the subgroups. We found a higher prevalence of HLA-B*58:01 genotyping in some Asian populations compared with the Whites. There is evidence to confirm a strong association between this allele and allopurinol-induced SCARs.

Background: Amniocentesis (AC) remains the most commonly performed prenatal invasive diagnostic test. The data available till now have been collected before the era of high-end ultrasound machines, NIPS, and chromosomal microarrays. In selected cases, whole-exome sequencing is also offered prenatally. The evolution of ultrasound, NIPS, and genetic testing has made us revisit this topic.Objective: We aimed to research and revisit AC data regarding the indications, procedures, genetic testing methods, and outcomes. We reinforce the knowledge of AC, offer tips to minimize complications, and help communicate and counsel patients based on the AC data.Methods: It was a retrospective study from October 2019 to March 2023 in a tertiary care fetal medicine center in a university hospital. A total of 321 patients who underwent AC were analyzed. We observed the demographic details, indications, procedure details, and maternal–fetal and neonatal outcomes.Results: During the study period, 321 patients underwent AC. Abnormal ultrasound findings (71%) were the most common indication for AC. Then, 9% (30/321) had abnormal genetic results. Down syndrome was the most common abnormality (14), followed by Edwards syndrome. Then, 47.96% of cases were in age > 35 years. We had three cases of bloody tap, one leak per vagina, and two missed abortions following AC. Then, 58% had live births.Conclusion: AC is a relatively safe procedure, and even with the advent of NIPS, it remains the gold standard prenatal diagnostic genetic testing method. Major structural anomalies and parental chromosomal anomalies are irreplaceable indications of AC. The technique and expertise of health professionals dictate the complication rate of that center. Chromosomal microarray, DNA storage, and whole-exome sequencing have added an extended armamentarium to our discovery of genetic diseases. Maternal and neonatal outcomes after AC are favorable, so do not hesitate to carry out this invasive test when indicated.

Non-invasive prenatal diagnosis (NIPD) for aneuploidy has been developed to overcome the limitations of non-invasive prenatal testing (NIPT). NIPT, which analyzes cell-free fetal DNA (cffDNA) in the maternal blood, can only detect a few aneuploidies, such as trisomies 13, 18, and 21. Trophoblast retrieval and isolation from the cervix (TRIC) is an alternative method that separates trophoblasts from endocervical cells using a Papanicolaou smear for NIPD. Here, we report the application of fetal cells obtained from the uterine cervix using a non-invasive cervical cytobrush during the first trimester of pregnancy for diagnosing trisomies 13, 18, and 21, and sex chromosome anomalies. Trophoblast cells were isolated from the cervical fluid samples of nine pregnant women diagnosed with aneuploidy between the 5th and 20th weeks of gestation using magnetic nanoparticles with a human leukocyte antigen-G antibody. Fluorescence in situ hybridization analysis of the isolated trophoblast cells identified aneuploidies in all nine samples, which was consistent with conventional prenatal genetic testing. The proportion of trisomic cells was between 14.35 and 23.8%, indicating that the isolated cells comprised some maternal cells. In summary, we successfully identified aneuploidies using TRIC, suggesting its potential as a non-invasive prenatal genetic testing method. However, the efficiency of recovering trophoblast cells from TRIC remains to be elucidated.

Primary mitochondrial myopathies (PMMs), a group of genetic mitochondrial oxidative phosphorylation disorders, primarily affect skeletal muscle function. No approved treatments for PMM exist, and patient information is limited. The international RePOWER registry (NCT03048617) assessed genotypic and phenotypic relationships in PMM and identified patients for MMPOWER-3 (elamipretide Phase 3 study). RePOWER enrolled screened and ambulatory patients aged 16-80 years. With signs and/or symptoms of PMM (N = 376; 60.4% female; mean [SD] age 42.6 [14.4] years; ~75% with an mtDNA variant and ~25% with an nDNA variant). Baseline information, current symptoms, qualityoflife, and functional assessments (6-Minute Walk Test [6MWT], Triple-Timed Up-and-Go [3TUG] Test, and 5-Times Sit-to-Stand Test [5XSST]) were captured. Accredited laboratory and genetic testing methods were available to most patients. The majority of enrolled PMM patients presented with progressive external ophthalmoplegia and fatigue. US patients were observed to use more medical interventions. Compared to non-US patients, US patients did not perform as well on the 6MWT (mean 364.6 vs. 375.2 m) and 5XSST (mean 21.6 vs. 18.6 s); US patients performed better on the 3TUG test (mean 40.2 vs. 45.0 s). The RePOWER registry provided data on patients with genetically confirmed PMM, thereby improving our understanding of PMM diagnosis and treatment and the differences in global mitochondrial clinical practice.

A global analysis of genetic testing methods for familial hypercholesterolemia; a study by the EAS-FH studies collaboration (FHSC)

To explore the genetic etiology of fetal skeletal dysplasia using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) techniques, and the feasibility of using WES as the first-tier method for such fetuses. Seventy four fetuses with skeletal dysplasia detected by prenatal ultrasound at the Genetic Testing Center of the Women and Children's Hospital Affiliated to Qingdao University from January 2020 to August 2024 were selected as the study subjects. Fetal muscle and peripheral blood samples of the pregnant women and their spouses were collected and subjected to WES analysis. CNV-seq was carried out on all fetal muscle tissue samples. And the results were compared with the CNVs indicated by WES. Genetic etiologies were analyzed across different subtypes of skeletal dysplasia. And the feasibility of using WES as the first-tier genetic test for similar fetuses was assessed, in addition with a systematic cost-effectiveness analysis. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: QFELL-YJ-2024-201). A total of 50 fetuses were diagnosed, which yielded a diagnostic rate of 67.57%. These included 6 chromosomal aneuploidies, 4 chromosomal CNVs and 40 monogenic disorders. The monogenic diseases had involved 46 variant sites in 23 pathogenic genes, among which 12 were unreported previously, including MYH3: c.735T>C, ALPL: c.1324C>T, NEK9: c.1973G>A, MAGEL2: c.2024_2025del, LMBR1: c.423+4914A>C, NEB: c.21273_21276del, COL1A1: c.2651G>C and c.2758G>C, ASPM: c.2473delinsGA, TBX5: c.704G>A, DYNC2H1: c.10893del, and DYNC2I2: c.1270C>T. Substantial concordance was reached between WES-derived CNV calls and CNV-seq findings. No clinically significant CNV was exclusively detected by CNV-seq. Cost-effectiveness modeling demonstrated that implementing WES as the first-tier genetic testing method could reduce the total expenditure when WES unit cost remained below 6.4 folds that of the CNV-seq. Genetic variants including single nucleotide variations (SNV) of monogenic disorders, chromosomal aneuploidies and genomic CNVs are important causes for fetal skeletal dysplasia. WES is an accurate and efficient method for analyzing the etiology of fetal skeletal dysplasia, particularly in those with a family history of similar phenotype or maternal history of adverse pregnancies.