Application of Clinical Genetics最新文献

{"title":"Identification of Novel Co-Occurring <i>ZNF711</i> and <i>SRCAP</i> Variants in a Child with Neurodevelopmental Disorders Through Exome Sequencing.","authors":"Tingting Liu, Mingtao Huang, Min Dai, Yixuan Liang, Cuiping Zhang, Jianxin Tan, Fengchang Qiao, Yan Wang","doi":"10.2147/TACG.S625023","DOIUrl":"10.2147/TACG.S625023","url":null,"abstract":"<p><strong>Background: </strong>Global developmental delay (GDD)/intellectual disability (ID) represent a group of neurodevelopmental disorders (NDDs) with onset in childhood with a global prevalence of 1-3%. The etiology of GDD/ID is complex, with genetic factors accounting for about half of cases. Exome sequencing (ES) has proven to be an effective diagnostic tool for genetically heterogeneous disorders such as GDD/ID. This study aims to identify the genetic etiologies using ES in a Chinese patient with NDD.</p><p><strong>Methods: </strong>Clinical data were collected through physical examination. Trio-ES was conducted to investigate the potential genetic causes, followed by Sanger sequencing for validation.</p><p><strong>Results: </strong>The proband exhibited facial dysmorphisms, motor and language development delay, ID, autism spectrum disorder, and attention-deficit hyperactivity disorder symptoms. Trio-ES identified a novel maternal inherited hemizygous nonsense variant c.205G>T (p.E69*) in <i>ZNF711</i>, and a novel <i>de novo</i> missense variant c.673C>T (p.R225C) in <i>SRCAP</i>. Both of variants were classified as likely pathogenic. Phenotype dissection revealed <i>ZNF711</i> dominated neurodevelopmental abnormalities (Intellectual developmental disorder, X-linked 97, XLID97) and <i>SRCAP</i> contributed to multisystemic manifestations (developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, DEHMBA).</p><p><strong>Conclusion: </strong>To our knowledge, this study reports the first case of concurrent <i>ZNF711</i> and <i>SRCAP</i> variants in China, expanding variant spectrum of both genes. It highlights the critical value of ES for detecting multi-gene variants in probands with complex phenotypes.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"19 ","pages":"625023"},"PeriodicalIF":2.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiological Findings and Genetic Rearrangements in Paediatric Patients with Acute Lymphoblastic Leukaemia.","authors":"Agata Rocka, Maria Suchcicka, Magdalena Maria Woźniak, Monika Lejman","doi":"10.2147/TACG.S621917","DOIUrl":"10.2147/TACG.S621917","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate differences in radiological phenotypes between B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) in pediatric patients and to assess their correlation with specific genetic alterations.</p><p><strong>Study design: </strong>A single-center retrospective cohort study was conducted including 144 pediatric patients (n = 115 B-ALL, n = 29 T-ALL) diagnosed with acute lymphoblastic leukemia. Comprehensive clinical, laboratory, and multi-modal imaging data (X-ray, computed tomography, magnetic resonance imaging, and ultrasonography) were analyzed. Radiological findings were correlated with molecular profiles, including <i>KMT2A, ETV6::RUNX1, BCR::ABL1, IKZF1</i>, and <i>CDKN2A/B</i> alterations. Principal outcomes included the prevalence of specific imaging features across leukemia subtypes and their association with genetic abnormalities. Statistical significance was assessed using appropriate comparative analyses.</p><p><strong>Results: </strong>T-ALL demonstrated a more aggressive, mass-forming phenotype, with significantly higher rates of superior mediastinal widening 41.67% (n = 10) and mediastinal masses on CT 38.1% (n = 8) compared with B-ALL 12.28% (n = 14) and 2.56% (n = 2), respectively; p < 0.01. In contrast, B-ALL more frequently presented with diffuse interstitial pulmonary opacities 42.31% (n = 33). T-ALL was also associated with greater systemic and central nervous system involvement, including a higher prevalence of ischemic lesions on MRI 62.5% (n = 5) vs 24.0% (n = 12) and inguinal lymphadenopathy 37.5% (n = 3). Molecular analysis showed that <i>KMT2A</i> rearrangements and <i>IKZF1</i> deletions were associated with disseminated disease, including pulmonary nodules and multi-organ infiltration. In B-ALL, <i>CDKN2A/B</i> deletions 31.3% (n = 36) were linked to hepatomegaly and inflammatory sinus changes.</p><p><strong>Conclusion: </strong>Distinct radiological patterns differentiate the space-occupying phenotype of T-ALL from the more heterogeneous presentation of B-ALL. The observed imaging-genetic associations are promising and hypothesis-generating. Although significant results have been obtained, it is necessary to conduct prospective multicenter cohorts. A multimodal diagnostic approach is essential for accurate disease characterization and individualized management in pediatric ALL.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"19 ","pages":"621917"},"PeriodicalIF":2.4,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preimplantation Genetic Testing for Cornelia de Lange Syndrome with Low-Level Maternal Gonadal Mosaicism for a Sub-Megabase Deletion in China.","authors":"Lulu Meng, Yan Wang, Junqiang Zhang, Ran Zhou, Xingxing Wang, Fengchang Qiao, Qinxin Zhang, Cheng Wan, Shujing Jiao, Ping Hu, Zhengfeng Xu","doi":"10.2147/TACG.S603242","DOIUrl":"10.2147/TACG.S603242","url":null,"abstract":"<p><strong>Purpose: </strong>To diagnose and perform preimplantation genetic testing for monogenic disorders (PGT-M) in a Chinese family affected by Cornelia de Lange syndrome type 5, resulting from a microdeletion in Xq13.1q13.2 truncating the <i>HDAC8</i> gene characterized by low-level gonadal mosaicism.</p><p><strong>Patients and methods: </strong>A de novo copy number variation (CNV) was identified through chromosomal microarray analysis and whole exome sequencing in a family with two unsuccessful pregnancies, indicating germline mosaicism. The CNV was validated via real-time quantitative PCR. Whole-genome low-coverage mate-pair sequencing was conducted on female peripheral blood to exclude chromosomal abnormalities. Long-PCR amplified the deleted fragment, utilizing primers designed nearby breakpoints identified through chromosomal microarray analysis. Oxford Nanopore Technology sequencing pinpointed specific breakpoint positions. Droplet-digital PCR (ddPCR) confirmed germline mosaicism in ovarian samples.</p><p><strong>Results: </strong>A female patient, suspected of harboring a de novo microdeletion at Xq13.1q13.2 exhibiting gonadal mosaicism, along with her husband, participated in this study. The diagnoses of the 172.3 kb microdeletion at Xq13.1q13.2 as low-level gonadal mosaicism was corroborated through nanopore sequencing and ddPCR. We constructed the high-risk haplotype using the affected products of conception as the phasing reference, and performed PGT-M based on SNP haplotype linkage analysis, finally achieving a healthy live birth in February 2023.</p><p><strong>Conclusion: </strong>Our findings underscore the efficacy of PGT-M employing haplotype linkage analysis for CNVs less than 1 Mb, even within cases involving gonadal mosaicism. We present methodologies to address microdeletions associated with gonadal mosaicism utilizing next-generation sequencing, microarray, nanopore sequencing and ddPCR techniques. Our results advocate for an expansion of PGT-M based on haplotype linkage analysis for families with minor pathogenic CNVs.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"19 ","pages":"603242"},"PeriodicalIF":2.4,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148593897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genealogical Identification and Short Tandem Repeat-Based Verification of Suspected Consanguinity in Mongolian Families.","authors":"Altansukh Tsend-Ayush, Suvd Tumurbaatar, Buyandelger Baatar, Erdenetuya Ganbaatar, Oyunsuren Davaasuren, Byambasuren Dagvajantsan, Myagmartseren Dashtseren, Tsolmon Unurjargal, Khurelbaatar Nyamdavaa, Sarantuya Jav, Battogtokh Chimeddorj","doi":"10.2147/TACG.S577541","DOIUrl":"10.2147/TACG.S577541","url":null,"abstract":"<p><strong>Purpose: </strong>The prevalence of consanguineous marriages remains high in several regions worldwide, particularly the Middle East and South Asia, with a reported rate of 58%. However, the prevalence and genetic characteristics of consanguineous marriages in Mongolia are not well studied. This study aimed to estimate the frequency of consanguineous marriages in selected Mongolian populations, using genealogical and short tandem repeat (STR) analyses.</p><p><strong>Patients and methods: </strong>This cross-sectional study was conducted at the Institute of Biomedicine at the Mongolian National University of Medical Sciences. A total of 574 individuals from 185 families across 43 soums in three provinces (X1, X2, and X3) were included. Genealogical analysis was used to construct pedigree-based consanguinity profiles, and STR analysis was performed to validate biological relatedness in selected families.</p><p><strong>Results: </strong>Seventeen families were consanguineous, with a mean inbreeding coefficient of 0.089 ± 0.136, whereas 42 families were classified as suspected consanguinity. Among the confirmed cases, seven families with complete biological samples were further analyzed using STR markers, of which five showed molecular evidence of consanguinity (probabilities, 76.18-98.84%). The STR analysis of 29 families classified as suspected or non-consanguineous identified 13 families as non-consanguineous and 10 families showing possible or indeterminate relatedness. Notably, six families initially classified as suspected or non-consanguineous demonstrated molecular evidence of consanguinity (probabilities, 70.75-99.85%). Genetic diversity analysis revealed reduced heterozygosity in offspring from consanguineous families (expected heterozygosity [HE] = 0.7580, observed heterozygosity[HO] = 0.7045) compared with offspring from non-consanguineous families (HE = 0.7858, HO = 0.8110), with a significant reduction in HO (<i>p</i> = 0.0009).</p><p><strong>Conclusion: </strong>This study demonstrates the value of integrating genealogical and STR-based molecular approaches for the assessment of consanguinity in Mongolia. Molecular analyses identified consanguineous relationships that were not evident from pedigree information alone and revealed reduced genetic diversity among offspring from consanguineous families. These findings provide important baseline data for understanding the genetic consequences of consanguinity in the Mongolian population and support the need for large scale epidemiological and genetic investigation.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"19 ","pages":"577541"},"PeriodicalIF":2.4,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13360830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148438449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generalized Nevus Lipomatosus Cutaneous Superficialis: A Case Report with Comprehensive Genetic Analysis.","authors":"Ye Qiu, Rina Su, Xiangxi Su, Yankun Zhang, Yaqi Tan, Xiuying Zhang, Fang Liu","doi":"10.2147/TACG.S592972","DOIUrl":"10.2147/TACG.S592972","url":null,"abstract":"<p><strong>Background: </strong>Nevus lipomatosus superficialis (NLS) is a rare cutaneous hamartoma characterized by ectopic adipose tissue in the dermis. Its genetic basis remains largely unknown.</p><p><strong>Methods: </strong>We conducted a comprehensive clinical, histopathological, and genetic investigation of a 17-year-old female with an exceptionally extensive distribution of lesions (involving trunk, buttocks, lower extremities, and vulva) that was atypical due to the presence of significant pain and recurrent infections. Whole exome sequencing (WES) was performed on the proband and both parents (trio-WES), and whole genome sequencing (WGS) was performed on fresh lesional tissue. Low-level mosaicism or regulatory mechanisms may remain undetected.</p><p><strong>Results: </strong>Physical examination revealed widespread hyperpigmented plaques. Histopathology confirmed mature adipocytes within the superficial to mid-dermis, consistent with NLS. Under our detection thresholds, we did not identify any pathogenic or likely pathogenic variants from WES or WGS. WES revealed 24 variants of uncertain significance, none of which were compelling for phenotype/pathway relevance. WGS did not identify pathogenic coding or non-coding variants, structural variations, copy number variations, or mitochondrial mutations. No pathogenic mutation was detected, suggesting alternative genetic mechanisms may be involved.</p><p><strong>Conclusion: </strong>This case represents a rare presentation of extensive NLS with associated pain. Comprehensive genetic analysis did not identify pathogenic variants under our detection thresholds, while suggesting possible somatic mosaicism, recessive inheritance, or non-coding region variations.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"19 ","pages":"592972"},"PeriodicalIF":2.4,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148431228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Deep-Intronic <i>CFAP44</i> Variant Underlies Multiple Morphological Abnormalities of the Sperm Flagella.","authors":"Yaxian Ma, Yuecheng Yang, Tong Zhang, Daoheng Hu, Yuancun Zhao, Xuancheng Mai, Junxue Ni, Jie Zhang","doi":"10.2147/TACG.S609696","DOIUrl":"10.2147/TACG.S609696","url":null,"abstract":"<p><strong>Purpose: </strong>Multiple morphological abnormalities of the sperm flagella (MMAF), uncommonly causing primary infertility, are typical features of aberrant spermatozoa flagellum morphologies, which manifest as shortness, absence, bending, coiling, and irregularity of flagella. <i>CFAP44</i>, an important component of flagella assembly, has attracted significant interest due to its critical role in MMAF pathogenesis. Understanding the variants associated with <i>CFAP44</i> can provide insights into the molecular mechanisms underlying MMAF.</p><p><strong>Patients and methods: </strong>A comprehensive clinical evaluation was conducted on an infertile Chinese male patient from a nonconsanguineous family with sever asthenozoospermia (no progressive sperm). By performing whole-exome sequencing (WES), a novel variant of <i>CFAP44</i> was identified. Sanger sequencing was performed to confirm the variant. To better investigate its pathogenicity, In silico variant analyses, minigene splicing assays and RT-PCR in vivo were performed.</p><p><strong>Results: </strong>As a result, a <i>CFAP44</i> homozygous deep-intronic variant (NM_001164496.1:c.1890+5G>C) was detected in the proband by WES. Sanger sequencing confirmed this variant in this family. Splice site prediction suggested that this variant may be a disease-causing variant. Then, exon 15 skipping was identified through minigene assays and RT-PCR in vivo, resulting in a 111-bp deletion within the mutated sequence, thereby indicating a disruption in the normal splicing of the <i>CFAP44</i> transcript.</p><p><strong>Conclusion: </strong>This is the first study to detect a homozygous variant (c.1890+5G>C) within the <i>CFAP44</i> gene causing MMAF in a Chinese family. Our results confirmed the pathogenicity of this deep-intronic variant and expanded the mutational spectrum of the <i>CFAP44</i> gene. Consequently, this study may help elucidate the effect of <i>CFAP44</i> on MMAF and provide a theoretical basis for MMAF.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"19 ","pages":"609696"},"PeriodicalIF":2.4,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precise Reproductive Counseling Enabled by Long-Read Sequencing in a Case of a <i>F8</i> Intron 1 Inversion and Duplication.","authors":"Yuying Yan, Pengzhen Jin, Lidan Xu, Ya Ma, Minyue Dong","doi":"10.2147/TACG.S606654","DOIUrl":"10.2147/TACG.S606654","url":null,"abstract":"<p><strong>Purpose: </strong>To demonstrate the clinical value of integrating next-generation sequencing (NGS) with long-read sequencing (LRS) for resolving complex <i>F8</i> variants and guiding personalized reproductive strategies in Haemophilia A (HA).</p><p><strong>Patients and methods: </strong>A patient with a history of three adverse pregnancy outcomes underwent comprehensive preconception genetic evaluation. NGS-based carrier screening initially excluded common single-gene disorders but flagged complex variants in the <i>F8</i> gene. Subsequent LRS was employed to characterize the specific structural variations.</p><p><strong>Results: </strong>NGS screening excluded 155 single-gene disorders and normal FMR1 repeats. LRS confirmed <i>F8</i> intron 1 inversion (Inv1) and a duplication variant, while ruling out intron 22 inversion. The patient was identified as an asymptomatic female carrier. Based on this diagnosis, reproductive counseling recommended spouse testing, preimplantation genetic testing for monogenic diseases (PGT-M) combined with aneuploidy screening (PGT-A), and prenatal diagnosis.</p><p><strong>Conclusion: </strong>This case underscores that while NGS is an effective screening tool, its limitations in detecting structural variations necessitate a stepwise diagnostic approach. Integrating LRS was indispensable for resolving complex <i>F8</i> variants, transforming ambiguous genetic signals into precise diagnoses. This precision serves as the cornerstone for accurate risk assessment and empowers couples with informed reproductive options, exemplifying a \"personalized reproductive blueprint\".</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"19 ","pages":"606654"},"PeriodicalIF":2.4,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Polymorphisms of Transforming Growth Factor Receptors (TGF-βRI, TGF-βRII) and Risk Factors Associated with Keloid Scars in Burkina Faso: A Cross-Sectional Study.","authors":"Koffi Agbessi Keto, Danielle Belemsigri, Serge Theophile Soubeiga, Marcelin Bonkoungou, Hadiaratou Nafore Badiala Gadiaga, Bibata Compaore, Pegdwinde Abel Sorgho, Albert Theophane Yonli, Wendkuuni Florencia Djigma, Jacques Simpore, Pascal Niamba","doi":"10.2147/TACG.S602982","DOIUrl":"10.2147/TACG.S602982","url":null,"abstract":"<p><strong>Background: </strong>The keloids scar is a skin scarring pathology with a higher frequency in the black population. Several genetic polymorphisms, including those of transforming growth factor receptors, have been identified as probable susceptibility genes. This study aimed to characterize the polymorphisms of <i>TGF-βRI, TGF-βRII</i> and identify risk factors associated with keloid scars in Burkina Faso.</p><p><strong>Methods: </strong>This was a cross-sectional study that included 141 subjects with keloids and conducted from April 2021 to April 2022. Genomic DNA was extracted using the \"PureLink^TM Genomic DNA Mini kit\". Genotyping of TGF-βRI rs111854391, rs121918710, and TGF-βRII rs104893807, rs28934568 polymorphisms was performed using real-time PCR. Results were considered statistically significant at p<0.05.</p><p><strong>Results: </strong>The average age of the study population was 34 ± 15 years and O Rhesus positive blood group (O+) was predominant (36.88%). All subjects (100%) were heterozygous (TG) for rs121918710. Medical or surgical history, family history, blood type, and rs28934568 polymorphism were related to the number of sites of keloids on the body. Patients with a medical history (9.8%) were carriers of the mutant allele C for rs28934568. Mossi ethnic had more than 8 times risk of developing a keloid scar (p=0.030; OR=8.66 (95% CI: 1.230-60.902).</p><p><strong>Conclusion: </strong>The presence in all the patients of the mutated allele for the <i>rs</i> 121918710 polymorphism could explain the involvement of this mutation in the occurrence of keloid scars. In addition, ethnicity and blood type were the risk factors associated with keloids.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"19 ","pages":"602982"},"PeriodicalIF":2.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13185948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Feasibility of Early First-Trimester Non-Invasive Prenatal Testing: Associations Between Gestational Age, Fetal Fraction, and No-Call Rates.","authors":"Trinh The Son, Sang Trieu Tien, Tran Van Khoa, Hung Sy Ho, Hien Le Thi Thu, Nhat Ngoc Nguyen, Dang Thai Son, Phong Nguyen Van, Minh Duc Pham, Hang Thi Doan","doi":"10.2147/TACG.S599716","DOIUrl":"10.2147/TACG.S599716","url":null,"abstract":"<p><strong>Background: </strong>Non-invasive prenatal testing (NIPT) based on cell-free fetal DNA (cffDNA) is widely used for screening common fetal aneuploidies. Although fetal fraction (FF) increases with gestational age, the feasibility and performance of NIPT in the early first-trimester, particularly before 10 weeks of gestation, remain incompletely defined.</p><p><strong>Methods: </strong>This retrospective cohort study included 9,708 singleton pregnancies undergoing first-trimester NIPT between 9 weeks 0 days and 13 weeks 6 days of gestation, which was determined by ultrasound using crown-rump length (CRL) measurement. Participants were stratified into two groups based on gestational age at testing (< 10 weeks and ≥ 10 weeks). Multivariable linear regression was used to assess factors associated with fetal fraction, and multivariable logistic regression was applied to evaluate predictors of no-call results (non-reportable NIPT outcome primarily attributed to fetal fraction <4%), adjusting for maternal age and body mass index (BMI).</p><p><strong>Results: </strong>Fetal fraction increased significantly with advancing gestational age. After adjustment for maternal age and BMI, testing performed at ≥ 10 weeks was associated with a higher fetal fraction compared with testing at < 10 weeks (β = 1.58; 95% CI, 1.31 to 1.85; <i>p</i> < 0.001). However, gestational age was not independently associated with the risk of a no-call result (adjusted OR 0.88; 95% CI, 0.68 to 1.16; <i>p</i> = 0.40), and no significant difference in no-call rates was observed between the two gestational age groups (3.78% vs. 3.76%).</p><p><strong>Conclusion: </strong>Although fetal fraction increases after 10 weeks of gestation, gestational age is not an independent determinant of no-call results once fetal fraction adequacy is achieved. NIPT performed in the early first-trimester (< 10 weeks of gestation) demonstrates acceptable analytical feasibility and reliable performance, supporting its use for early prenatal screening under appropriate clinical conditions.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"19 ","pages":"599716"},"PeriodicalIF":2.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes and Management of Pregnancies Screening Positive for Microdeletions 22q11.2, 15q11.2, 1p36, 4p, or 5p: A Retrospective Cohort Study.","authors":"D Claire Miller, Devika Chawla, Summer Pierson, Katherine Johansen Taber","doi":"10.2147/TACG.S591410","DOIUrl":"10.2147/TACG.S591410","url":null,"abstract":"<p><strong>Purpose: </strong>To compare pregnancy outcomes and management between patients screening positive for five microdeletions (microdeletion screen-positive, MDS+) and patients screening negative (microdeletion screen-negative, MDS-).</p><p><strong>Patients and methods: </strong>Patients who received a prenatal cell-free DNA (pcfDNA) test that screens for microdeletions 22q11.2, 15q11.2, 1p36, 4p, and 5p and results were linked to de-identified insurance claims. Diagnosis and procedure codes were used to assess outcomes. Logistic and Poisson regression with adjustment for prior high-risk pregnancy and payer type were used to compare pregnancy outcomes and management in those with MDS+ and MDS- results.</p><p><strong>Results: </strong>A total of 119 MDS+ patients and 287,169 MDS- patients were eligible for analysis. During pregnancy, MDS+ patients were more likely than MDS- patients to have polyhydramnios (18.5% in MDS+ vs. 3.4% in MDS-; OR=6.3 [95% CI: 3.8-10.1]; p<0.001) and fetal growth restriction (22.2% in MDS+ vs. 10.4% in MDS-; OR=2.4 [95% CI: 1.5-3.7]; p<0.001). MDS+ patients were more likely to experience pregnancy loss (OR=3.2; 95% CI: 1.3-6.3; p=0.004) or terminate the pregnancy (OR=22.2 [95% CI: 8.6-46.8]; p<0.001). Among patients with a live birth, MDS+ were more likely to have a preterm delivery (25.0% in MDS+ vs. 15.4% in MDS-; OR=1.8 [95% CI: 1.0-3.0]; p=0.04). MDS+ patients had increased pregnancy management, including more invasive diagnostic testing (13.4% in MDS+ vs. 0.5% in MDS-; OR=31.0 [95% CI: 17.5-51.1]; p<0.001) and more frequent echocardiograms (RR=1.5 [95% CI: 1.2, 1.9]; p<0.001) compared to MDS- pregnancies.</p><p><strong>Conclusion: </strong>MDS+ pregnancies had elevated rates of ultrasound abnormalities, pregnancy loss, preterm birth, and pregnancy management as compared to an MDS- control group. These findings support the clinical utility of microdeletion screening in prenatal care.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"19 ","pages":"591410"},"PeriodicalIF":2.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147784239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}