Application of Clinical Genetics最新文献

{"title":"The Impact of FSHR Polymorphisms (rs6165 and rs6166) on Ovarian Response to Stimulation in Infertile Women with Diminished Ovarian Reserve.","authors":"Thuy Thi Thanh Hoang, Son The Trinh, Nhat Ngoc Nguyen, Minh Nguyet Ho, Minh Dinh Pham, Nhung Thi Hoang, Sang Tien Trieu, Hung Sy Ho","doi":"10.2147/TACG.S528567","DOIUrl":"10.2147/TACG.S528567","url":null,"abstract":"<p><strong>Background: </strong>Diminished ovarian reserve (DOR) remains a significant challenge in IVF, as it is closely associated with poor ovarian response. Beyond well-established predictive of ovarian response, genetic polymorphisms in the FSH receptor (FSHR) gene rs6165 and rs6166 have been reported as potential markers.</p><p><strong>Purpose: </strong>Evaluating the expression of FSHR rs6165 and rs6166 in DOR patients and their impact on ovarian response to stimulation.</p><p><strong>Materials and methods: </strong>This prospective cross-sectional included 79 DOR patients (AMH < 1.2 ng/mL and/or AFC < 5) undergoing IVF treatment at the National Hospital of Obstetrics and Gynecology, Vietnam. GnRH antagonist protocol was applied, using alpha follitropin with individualized dosages combined with clomiphene citrate, followed by dual-trigger ovulation induction. FSHR rs6165 and rs6166 were genotyped by Next-Generation Sequencing (NGS) assays, with Sanger sequencing for validation. Ovarian response was assessed based on follicular development and oocyte retrieval.</p><p><strong>Results: </strong>The overall prevalence of the rs6165 and rs6166 polymorphisms was 10.1% (8/79), with strong linkage disequilibrium observed between the two loci (OR = 490, p < 0.0001). No significant differences in age, AMH, baseline FSH, and AFC were found in all genotypes (AA, AG, GG) of rs6165 and rs6166. In the rs6165 dominant model, patients with G alleles (AG/GG) had lower total oocyte retrieval, FOI and FORT than the AA genotype. In rs6166 codominant, dominant, and recessive models, the GG phenotype retrieved fewer oocytes (p1 = 0.02, p2 = 0.03, p3 = 0.01). FORT was significantly lower in G allele carriers (AG/GG) than AA (p = 0.04).</p><p><strong>Conclusion: </strong>In the diminished ovarian reserve patients, FSHR rs6165 and rs6166 were associated with ovarian response to stimulation in IVF treatment. Specifically, the presence of G alleles in both rs6165 and rs6166 was correlated with reduced oocyte retrieval, independent of baseline ovarian reserve markers.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"18 ","pages":"119-129"},"PeriodicalIF":2.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650871","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":"Coexistence of Hereditary Hemorrhagic Telangiectasia and Moyamoya Disease: A Case Report Highlighting a Potential Genetic Synergy.","authors":"Shengyang Liu, Linghui Meng, YuZhu Wan, Shanfeng Liu, Li Shi","doi":"10.2147/TACG.S536913","DOIUrl":"10.2147/TACG.S536913","url":null,"abstract":"<p><p>Hereditary hemorrhagic telangiectasia (HHT) coexisting with moyamoya disease (MMD) is exceptionally rare. We report the first case of a 45-year-old female harboring two genetic variants implicated in vascular disease: a pathogenic mutation in ACVRL1 (c.1231C>T, p.Arg411Trp) and a novel variant of uncertain significance in RNF213 (c.13685C>T, p.Pro4562Leu). This case is remarkable for the concurrent manifestation of HHT-associated peripheral telangiectasia and MMD-characteristic intracranial arterial stenosis, suggesting a possible synergistic interaction between variants affecting distinct vascular signaling pathways. These findings offer new insights into the genetic mechanisms underlying complex hereditary vascular disorders and emphasize the importance of comprehensive genetic testing in diagnosing atypical vascular phenotypes.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"18 ","pages":"113-117"},"PeriodicalIF":2.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638351","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 Systematic Review of SNPs Screening for Platinum-Related Pharmacodynamics and Pharmacokinetics Genes in Non-Small Cell Lung Cancer for Precision Medicine.","authors":"Nadiya Nurul Afifah, Annisa Lazuardi Larasati, Indra Wijaya, Neily Zakiyah, Ruri Intania, Hideru Obinata, Melisa Intan Barliana","doi":"10.2147/TACG.S518467","DOIUrl":"10.2147/TACG.S518467","url":null,"abstract":"<p><strong>Introduction: </strong>Traditional treatments for non-small cell lung cancer (NSCLC), such as chemotherapy, especially platinum-based regimens, often lack efficacy due to the disease's inherent heterogeneity. Precision medicine in NSCLC recognizes each tumor's unique genetic profile. Alterations in the pharmacokinetics and pharmacodynamics of platinum-based therapies significantly influence their clinical outcomes. Previous research has predominantly focused on genetic polymorphisms in genes like <i>Glutathione S-transferase Pi 1 (GSTP1), ATP Binding Cassette subfamily C member 2 (ABCC2), Excision repair cross-complementation group 1 and 2 (ERCC1, and/ ERCC2</i>), which play crucial roles in detoxification, drug transportation, and Nucleotide Excision Repair (NER). However, findings have shown considerable variability.</p><p><strong>Methods: </strong>The analysis followed the PRISMA and STROPS Guidelines, using specific search terms including NSCLC, Chemotherapy, Polymorphisms, Single Nucleotide Polymorphisms (SNPs), <i>ERCC1, ERCC2, ABCC2, GSTP1</i>, Effectiveness, and Clinical Response. These studies were subjected to full-text screening process.</p><p><strong>Results: </strong>Initial screening of 370 studies, comprising 275 from PubMed and 95 from EBSCO, identified 53 relevant ones, excluding those such as reviews, non-English studies, and meta-analyses. Among the genetic variants studied (ERCC1 rs11615, ERCC2 rs13181, ABCC2 rs717620, GSTP1 rs1695), GSTP1 rs1695 emerged as particularly promising, with 11 studies indicating a significant association with improved survival outcomes.</p><p><strong>Conclusion: </strong>The integration of SNP profiling into clinical decision-making processes holds substantial potential for enhancing the personalization of NSCLC treatment strategies, thereby improving patient outcomes.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"18 ","pages":"93-112"},"PeriodicalIF":2.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555257","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 and QF-PCR Performance Evaluation of 20 Autosomal STR Loci on Chromosomes 13, 18, and 21 in Prenatal Diagnosis Among East Chinese Han Population.","authors":"Yingwen Liu, Jiangyang Xue, Lulu Yan, Changshui Chen, Shumin Zhao, Haibo Li","doi":"10.2147/TACG.S521043","DOIUrl":"10.2147/TACG.S521043","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the system performance of the 20 autosomal short tandem repeats (STR) polymorphic genetic loci in quality control for prenatal diagnosis.</p><p><strong>Methods: </strong>A genotyping system consisting of 6 STRs on chromosome 13 (chr13), 6 STRs on chromosome 18 (chr18), 8 STRs on chromosome 21 (chr21), and 10 genetic markers on sex chromosomes were used to analyze the genetic profiles of 2333 unrelated adult females from the Han population in East China. The population allele frequencies of the 20 autosomal STRs were obtained using the genotype dataset of the cohort. The established method in forensic genetic fields was used to calculate allele frequencies of the 20 autosomal STRs, observed heterozygosity (<i>H_obs</i> ), expected heterozygosity (<i>H</i>), random match probability (<i>PM</i>), power of non-parental exclusion in duos (<i>PE_duos</i> ), cumulative random match probability (<i>CPM</i>), and cumulative non-parental exclusion rate in duos (<i>CPE_duos</i> ). The possible influence of STR markers on the detection rates of heterozygotes was assessed by employing the binomial distribution approach for every autosomal chromosome.</p><p><strong>Results: </strong>The average expected heterozygosity for the STRs on chr13, chr18, and chr21 is 0.8097, 0.7478, and 0.7760, respectively. The <i>CPM</i> for the STRs on the three chromosomes is 4.52E-08, 7.34E-07, and 9.30E-10, respectively. The probability of detecting at least one heterozygosity on each chromosome is 0.999952, 0.999742, and 0.999994, respectively. The <i>CPE_duos</i> of the 20 STRs is 0.999982. And the potential linkage effects among the STRs on the autosomal have a negligible impact on the observed heterozygosity.</p><p><strong>Conclusion: </strong>The 20 autosomal STRs in the 30 plex genotyping system exhibit high polymorphism in the Han population from East China, effective meeting the quality control criteria and providing valuable guidelines in assessing the molecular karyotypes of the chromosomes for prenatal diagnosis.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"18 ","pages":"81-91"},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318294","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":"Intramuscular Vitamin B12 Treatment in Transcobalamin II Deficiency: Case Series Clinical Outcomes.","authors":"Ali M Sawlan, Msaed Alotaibi, Rayan M Alharbi, Nimr A Alwahbi, Manar Alshammary, Ali Mohammad Alasmari, Fuad Al Mutairi","doi":"10.2147/TACG.S519631","DOIUrl":"10.2147/TACG.S519631","url":null,"abstract":"<p><strong>Background: </strong>Transcobalamin II (TC II) deficiency is a rare autosomal recessive disorder that typically manifests in early infancy. Symptoms include failure to thrive, vomiting, weakness, and pancytopenia. If left undiagnosed and untreated, it can be life-threatening. TC II is crucial for transporting cobalamin (vitamin B12), which plays a vital role in homocysteine and methylmalonic acid metabolism. It serves as a cofactor in neurotransmitter synthesis and protein methylation processes.</p><p><strong>Methods: </strong>In this study, we reviewed the clinical presentation, treatment approaches, and long-term outcomes of four patients with confirmed TC II deficiency. All subjects were born to consanguineous parents and exhibited symptoms between birth and four months of age.</p><p><strong>Results: </strong>All patients presented with hematological abnormalities, elevated methylmalonic acid (MMA), and increased total homocysteine (tHcy) levels. Whole Exome Sequencing (WES) confirmed TC II deficiency in all cases, revealing diverse mutation spectra, primarily frameshift mutations (leu320Valfs*51, and IIe330Hisfs*9). No clear genotype-phenotype correlations were observed. The majority of patients were treated with intramuscular hydroxocobalamin (OH-Cbl), resulting in clinical and biochemical improvements.</p><p><strong>Conclusion: </strong>This study underscores the importance of early detection and appropriate management of TC II deficiency to prevent permanent morbidity and potentially fatal outcomes. Regular monitoring of clinical and neurological status, as well as MMA and tHcy levels, is essential to ensure adequate therapy. Intramuscular treatment is the preferred route to prevent neurological deficits and optimal markers normalization.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"18 ","pages":"73-80"},"PeriodicalIF":2.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267556","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 EBP c.452A>G Mutation Identified in a Girl with Conradi-Hünermann-Happle Syndrome Presenting with Hydronephrosis.","authors":"Fengchang Qiao, Huasha Zeng, Cuiping Zhang, Yan Wang, Yuguo Wang, Ran Zhou, Lulu Meng, Ping Hu, Zhengfeng Xu","doi":"10.2147/TACG.S513953","DOIUrl":"10.2147/TACG.S513953","url":null,"abstract":"<p><strong>Background: </strong>Conradi-Hünermann-Happle syndrome (CDPX2, OMIM 302960) is an X-linked dominant inherited disorder caused by variants in the <i>EBP</i> gene, which primarily affects the skin, bones, and eyes.</p><p><strong>Objective: </strong>To describe the clinical manifestations and genetic mutation in a 7-year-old girl presenting with severe scoliosis, hydronephrosis, and other skeletal abnormalities.</p><p><strong>Methods: </strong>The patient's medical history was collected from birth. Exome sequencing was performed to identify candidate genes, and the detected variant was confirmed by Sanger sequencing.</p><p><strong>Results: </strong>Exome sequencing revealed a de novo <i>EBP</i> mutation (c.452A>G, p.Gln151Arg) in the patient.</p><p><strong>Conclusion: </strong>The patient was diagnosed with X-linked chondrodysplasia punctata type 2 (CDPX2). This novel missense mutation expands the mutation spectrum of CDPX2 and underscores the clinical utility of exome sequencing in diagnosing this condition.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"18 ","pages":"63-72"},"PeriodicalIF":2.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095335","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":"The Frequency of <i>CYP2C19*2</i> Gene Polymorphisms in Burkina Faso Patients Treated with Clopidogrel.","authors":"Yves Donald Kagambèga, Abdoul Karim Ouattara, Teega-Wendé Clarisse Ouédraogo, Lassina Traoré, Nobila Valentin Yaméogo, Jacques Simpore","doi":"10.2147/TACG.S509095","DOIUrl":"https://doi.org/10.2147/TACG.S509095","url":null,"abstract":"<p><strong>Purpose: </strong>The hepatic cytochrome P450 2C19 (CYP2C19) superfamily plays a crucial role in converting clopidogrel into its active form. Polymorphisms in <i>CYP2C19</i> significantly contribute to the interindividual variability observed, often resulting in persistent thromboembolic complications. This study aimed to assess the frequency of the <i>CYP2C19*2</i> (<i>rs4244285</i>, 681 G>A1) polymorphism among patients with cardiovascular diseases undergoing clopidogrel therapy.</p><p><strong>Patients and methods: </strong>This cross-sectional study recruited a total of seventy-three (73) patients from the Cardiology Department of the Centre Hospitalier Universitaire Yalgado Ouédraogo (CHU-YO) between January and June 2023. DNA was extracted from blood samples for <i>CYP2C19*2</i> genotyping using PCR-RFLP.</p><p><strong>Results: </strong>Genetic analysis revealed frequencies of 65.8% for the wild-type CYP2C19*1/*1, 28.8% for the heterozygous CYP2C19*1/*2, and 2.7% for the homozygous variant CYP2C19*2/*2. The distribution of the genotypic frequencies was consistent with Hardy-Weinberg equilibrium (p> 0.05). The overall frequency of the <i>CYP2C19*2</i> allele in the study population was 16.4%, with 12.5% observed in females and 19.5% in males.</p><p><strong>Conclusion: </strong>This study provides valuable insights into the frequency of the CYP2C19*2 polymorphism among cardiovascular patients in Burkina Faso, contributing to the limited data available on <i>CYP2C19</i> polymorphisms in sub-Saharan Africa. The presence of loss-of-function alleles suggests a potential risk for reduced drug efficacy in a subset of individuals. As one of the pioneering studies in the region, these findings emphasize the importance of further research to understand the clinical implications of <i>CYP2C19</i> polymorphisms.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"18 ","pages":"55-61"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003331","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":"NIPT of Maternal Plasma-Originated cfDNA: Applications and Guide for the Implementation.","authors":"Fco Javier Fernández Martínez, M Mar Gil Mira, Cristina González González, Irene Madrigal Bajo, Raluca Oancea Ionescu, Carmen Orellana Alonso","doi":"10.2147/TACG.S451444","DOIUrl":"https://doi.org/10.2147/TACG.S451444","url":null,"abstract":"<p><p>The implementation of non-invasive prenatal testing (NIPT) in maternal plasma, based on cell-free DNA (cfDNA) analysis, has progressed over the last two decades and is now integrated into the Spanish National Health System. However, there remains significant heterogeneity in its indications, technical methodologies, and reporting standards, reflecting international variability. This guide, developed by experts from the Spanish Association of Prenatal Diagnosis (AEDP) and the Spanish Association of Human Genetics (AEGH), provides recommendations to standardize NIPT application. It addresses key aspects such as technical and analytical requirements, integration with invasive diagnostic methods, pre- and post-test genetic counseling, and legal considerations. Additionally, the guide discusses the detection of common aneuploidies, the limitations in identifying structural chromosomal abnormalities and rare variants, and the impact of biological and clinical factors on test performance. By establishing a minimum framework based on scientific evidence, this document aims to optimize NIPT implementation in a cost-effective manner, ensuring clinical validity and informed decision-making for both healthcare professionals and pregnant women.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"18 ","pages":"41-53"},"PeriodicalIF":2.6,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020328","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":"Survey of Structural Autosomal Abnormalities and Autosomal Variants in Infertile Patients Treated at Some IVF Centers in Vietnam.","authors":"Sang Tien Trieu, Minh Duc Pham, Hoang Le, Hien Van Vo, Phong Van Nguyen, Tuan Van Tran, Nhat Ngoc Nguyen, Son The Trinh","doi":"10.2147/TACG.S510933","DOIUrl":"https://doi.org/10.2147/TACG.S510933","url":null,"abstract":"<p><strong>Background: </strong>Chromosomal abnormalities and variations are significant contributors to reproductive challenges. This study aims to investigate the types and incidence of structural autosomal anomalies and autosomal variations in a large Vietnamese population undergoing infertility treatment.  .</p><p><strong>Material and methods: </strong>A retrospective analysis was conducted on 19,191 females and 18,584 males who needed assisted reproductive technology (ART) at the Military Institute of Clinical Embryology and Histology, and Andrology and Fertility Hospital of Hanoi from 2020 to 2023. Karyotyping was conducted using the G-band staining method, and the data were analyzed with STATA 16.0 software.</p><p><strong>Results: </strong>Males have a higher overall occurrence of structural autosomal anomalies, with a total of 359 cases (1.932%) compared to 306 cases (1.594%) in females, particularly inversions and robertsonian translocations. Chromosome 9 inversions were equally observed in both genders, while robertsonian translocations and reciprocal translocations were more frequent in males (0.183% and 0.468%, respectively) than in females (0.146% and 0.406%, respectively). Deletions and duplications were more prevalent in males, occurring at rates of 0.215% and 0.016%, respectively, versus 0.036% and 0.021% in females. Total autosomal variants were 1478 (7.953%) in males and 1864 (9.7%) in females. Chromosome 9 exhibits the highest occurrence of the q+/qh+ variant, followed by the one of chromosome 1 and chromosome 16. Chromosomes 21 and 22 show notable numbers of ps+ and pstk+ variants.  .</p><p><strong>Conclusion: </strong>Structural autosomal anomalies and autosomal variations are common in Vietnamese patients undergoing infertility, highlighting the necessity of genetic testing, particularly karyotyping, in the evaluation and management of infertility.   .</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"18 ","pages":"29-40"},"PeriodicalIF":2.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989823","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":"Associations of Karyotype and Age at Diagnosis with Physical Features and Comorbidities in Turner Syndrome: A Single-Site Experience.","authors":"Beáta Vida, Olga Török, Enikő Felszeghy, Mónika Orosz, Zoárd Tibor Krasznai, Zoltán Tándor, Attila Jakab, Tamás Deli","doi":"10.2147/TACG.S492592","DOIUrl":"10.2147/TACG.S492592","url":null,"abstract":"<p><strong>Aim: </strong>Turner syndrome (TS) is one of the most common genetic diseases in females, with typical physical features and comorbidities. Karyotype-phenotype associations and clinical significance of childhood versus adolescent/adulthood diagnosis are conflicting.</p><p><strong>Purpose: </strong>Determining the role of certain TS karyotypes and early (<12 years of age) vs late (≥12 years) diagnosis in TS-specific phenotype and comorbidity penetrance.</p><p><strong>Patients and methods: </strong>Retrospective analysis of baseline characteristics and 45 TS-specific features and comorbidities of 75 TS patients were diagnosed between 2009 and 2019 and followed-up until 2023 in our tertiary care center.</p><p><strong>Results: </strong>Thirteen different karyotypes were detected: 45,X,inv(10), 45,X,inv(9)(15), 45,X, 46,X,i(Xq), 46,X,del(Xp), 46,XX,del(X)q21, 45,X/46,X,del(X), 45,X/46,X,+mar, 45,X/46,X,rX, 45,X/46,XX, 45,X/46,XY, 45,X/47,XXX, 46,X,i(Xq)/47,XX,i(Xq). The classic karyotype with 45X monosomy showed an increased risk for hypertrichosis (28.6% vs 7.5%, OR 4.93, 95% CI [1.23-19.73]), pterygium colli (34% vs 12%, OR 3.65, 95% CI [1.13-11.75]) and short stature (91% vs 75%, OR 3.56 [0.89-14.17]. Mosaic karyotypes had a smaller risk of pterygium colli (OR 0.28 [0.073-1.092]) and short stature (OR 0.29 [0.086-1.026]. 45X/46XX mosaicism was associated with an increased risk of hypertension (33% vs 6%, OR 7.75 [1.39-43.08]), and the presence of the iso (Xq) chromosome increased the risk of celiac disease (28% vs 3%, OR 13.2 [1.52-114.52]). 44/75 (58.6%) of the cohort were diagnosed at <12 years of age. In the <12-year-old diagnosis group, facial dysmorphism and low hairline, (OR 3.30, [1.26-8.65]), low-set ears (OR 2.51 [0.98-6.46]), and breasts abnormalities (OR 4.71 [1.72-12.83]), short stature (OR 4.09 [1.13-14.82]) and GH therapy (OR 4.93 [1.31-16.01]) occurred more frequently. If diagnosed <12 years, patients had a decreased risk of hepatosplenomegaly (OR 0.10 [0.02-0.50]) and hypertension (OR 0.097 [0.01-0.85]).</p><p><strong>Conclusion: </strong>TS patients should be handled as a heterogenous group, as they seem to differ in the penetrance of phenotypical features of the disease and the risk of comorbidities depending on karyotype and age at diagnosis.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"18 ","pages":"9-27"},"PeriodicalIF":2.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450530","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}