American Journal of Medical Genetics Part C: Seminars in Medical Genetics最新文献

{"title":"The Impact of Karyotype on Congenital Heart Diseases in Turner Syndrome: A Systematic Review and Meta-Analysis.","authors":"Francisco Álvarez-Nava, Melissa L Crenshaw, Ivonne Bedei, Marisol Soto, Andréa T Maciel-Guerra, Anne Skakkebæk","doi":"10.1002/ajmg.c.32146","DOIUrl":"https://doi.org/10.1002/ajmg.c.32146","url":null,"abstract":"<p><p>It is evident that Turner syndrome (TS) impacts almost all developmental stages of the fetal heart with congenital heart disease (CHD) being seen in 23%-50% of individuals. Although the spectrum of CHDs in TS is well-established, with left-sided lesions predominating, the influence of specific karyotypes on the prevalence and types of CHDs remains incompletely understood. The primary objective of this systematic review/meta-analysis was to quantitatively synthesize the existing evidence on the association between specific karyotypes in TS and the risk of various CHDs. A systematic literature search was conducted through December 2023 to identify studies reporting the prevalence of CHDs in relation to TS karyotype. The quality of the individual studies was assessed using the Joanna Briggs Institute critical appraisal tools for systematic reviews. The overall estimates were pooled using both fixed- and random-effects models. Sensitivity and subgroup analysis were performed. Twenty-five studies were included in the analysis. TS individuals with a 45,X karyotype showed a significantly higher likelihood of bicuspid aortic valve (BAV) (pooled OR, 3.14 [95% CI: 2.49-3.94]), aortic coarctation (CoA) (pooled OR, 4.16 [95% CI: 2.74-6.31]), and partial anomalous pulmonary venous return (PAPVR) (pooled OR, 4.86 [2.31-10.2]) compared with TS individuals with a non-45,X karyotype. In addition, TS individuals with a 45,X karyotype also showed a significantly higher likelihood of BAV (pooled OR, 2.72 [95% CI: 1.62-4.56]) when compared with TS individuals with 45,X/46,XX mosaicism. TS individuals with a 45,X karyotype showed a significantly higher risk of BAV (pooled OR, 2.13 [95% CI: 1.42-3.21]) and CoA (pooled OR, 4.52 [95% CI: 1.58-13.0]) when compared with TS individuals with an isochromosome Xq. A significantly higher likelihood of BAV was also found in 45,X compared to other karyotypes (e.g., 45,X/46,XY and TS karyotypes with ring X chromosome). Some heterogeneity was evident, but publication was low. This meta-analysis confirms a strong association between the 45,X karyotype and increased prevalence of BAV, CoA, and PAPVR in TS. While 45,X/46,XX mosaicism and karyotypes with an isochromosome Xq mitigate risk, the findings emphasize the need for large-scale studies to refine risk assessment and management strategies.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32146"},"PeriodicalIF":2.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Review of Myhre Syndrome.","authors":"Maggie R Brand, Ryan Monsberger, Robert J Hopkin, Angela E Lin","doi":"10.1002/ajmg.c.32145","DOIUrl":"https://doi.org/10.1002/ajmg.c.32145","url":null,"abstract":"<p><p>This research review of Myhre syndrome is a summary of published articles which provide a valuable resource for readers, researchers, and future authors. It traces the evolution of the Laryngotracheal-Arthropathy-Prognathism-Short Stature (LAPS) syndrome to the current eponym of Myhre syndrome. These allelic disorders are caused by pathogenic variants in SMAD4. After the initial report over 40 years ago, the steady publication of case reports and small series was accelerated following the discovery of the pathogenic variants in SMAD4. The articles in this review include numerous case reports and small series, reports about basic science, the discovery of the causative gene, the emergence of the natural history in larger studies, and articles about specific features, especially the cardiovascular system and airways. We hope this analysis provides a foundation for future research that may extend symptom-based treatment to genetic-based therapy.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32145"},"PeriodicalIF":2.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualizing Turner Syndrome.","authors":"Kirstine Stochholm, Astrid Bruun Rasmussen, Anne Skakkebæk","doi":"10.1002/ajmg.c.32144","DOIUrl":"https://doi.org/10.1002/ajmg.c.32144","url":null,"abstract":"<p><p>Turner syndrome (TS) continues to present a diagnostic challenge to healthcare professionals. The diagnostic challenges associated with TS result in delayed treatment and clinical care. Here we provide an update of the physical appearance of girls and women with TS by presenting clinical photographs and detailed clinical descriptions of 25 Danish girls and women with TS. Our data highlight the wide variation in physical appearance and clinical phenotype seen in girls and women with TS.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32144"},"PeriodicalIF":2.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Table of Contents, Volume 199, Number 1, March 2025","authors":"","doi":"10.1002/ajmg.c.32091","DOIUrl":"https://doi.org/10.1002/ajmg.c.32091","url":null,"abstract":"","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"199 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover Image, Volume 199, Number 1, March 2025","authors":"","doi":"10.1002/ajmg.c.32143","DOIUrl":"https://doi.org/10.1002/ajmg.c.32143","url":null,"abstract":"<p>From Stochholm et al. 2025. “Vizualizing Turner Syndrome.” <i>American Journal of Medical Genetics Part C: Seminars in Medical Genetics</i>: e32144. doi:10.1002/ajmg.c.32144. Photographs of individuals with Turner syndrome. Reproduced with permission from the patients and, where applicable, their legal guardians.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"199 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment From the Guest Editors","authors":"Melissa L. Crenshaw,&nbsp;Anne Skakkebæk","doi":"10.1002/ajmg.c.32141","DOIUrl":"10.1002/ajmg.c.32141","url":null,"abstract":"","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"199 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Genomic Analysis of Usher Syndrome: Population-Scale Prevalence and Therapeutic Targets.","authors":"Shelby E Redfield, Stephanie A Mauriac, Gwenaëlle S Géléoc, A Eliot Shearer","doi":"10.1002/ajmg.c.32142","DOIUrl":"https://doi.org/10.1002/ajmg.c.32142","url":null,"abstract":"<p><p>Usher syndrome, the most common form of deaf-blindness, displays extensive genetic, allelic, and phenotypic heterogeneity. The dual sensory impairment associated with this autosomal recessive disorder makes Usher syndrome an important target for gene therapy, with dozens of published preclinical studies targeting multiple Usher syndrome genes and using multiple gene therapy strategies. Nine genes have been conclusively linked to Usher syndrome; however, data on the prevalence and contribution of specific genetic variants is lacking. Such information is essential to choosing a favorable target gene or therapeutic approach during clinical trial design. Here, we used large genomic databases to systematically evaluate the genomics of Usher syndrome. We ascertained pathogenic Usher syndrome variants from three clinical databases and determined the occurrence of these pathogenic Usher syndrome variants within: (1) a publicly available dataset including worldwide populations (GnomAD), (2) a cohort of 3888 children without hearing loss, and (3) 637 children with hearing loss. Results show significant variability in the frequency of Usher syndrome variants by gene and genetic ancestry. 1% of control subjects carry a pathogenic USH variant. Pathogenic variants in USH2A are the most prevalent, at 1 in 150 individuals (0.0062). Calculated general population prevalence for all Usher syndrome subtypes is 1 in ~29,000, indicating that 30,405 individuals in the United States and 721,769 individuals worldwide are affected. We estimate that 324 babies in the United States and 12,090 worldwide are born with Usher syndrome each year. We identify key targets for genetic therapy based on population-level prevalence including a focus on alternatives to gene replacement therapies, specifically for USH2A.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32142"},"PeriodicalIF":2.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parental Decision-Making Following a Prenatal Diagnosis of Turner Syndrome: A Systematic Review.","authors":"Inger Lily Hjuler Dorf, Stina Lou, Anne Skakkebæk","doi":"10.1002/ajmg.c.32140","DOIUrl":"https://doi.org/10.1002/ajmg.c.32140","url":null,"abstract":"<p><p>This systematic review investigates factors influencing parental decision-making following a prenatal diagnosis (PND) of Turner syndrome (TS), aiming to enhance the foundation for tailored and supportive genetic counseling. A comprehensive literature search was conducted in the medical databases PubMed, Embase, and CINAHL. The selection of studies was guided by specific eligibility criteria. Extracted data was arranged in a review matrix, and study quality was assessed using a methodological quality score (MQS). Twenty-seven studies were selected for review, including 21 retrospective studies, five case reports, and one prospective study. The mean MQS across studies was 9.7 points (low to moderate). Across the included studies, nine categories of factors were investigated in association with parental decisions, including five pregnancy-related categories (ultrasound-detected abnormalities, karyotype, gestational age at diagnosis, time period of diagnosis, and prenatal counseling) and four categories related to expectant parents (age, reproductive history, expectations/concerns about the child's prognosis, and socio-demographic characteristics). Among these, ultrasound-detected abnormalities, karyotype, and counseling emerged as key factors influencing parental decisions. Parental decisions following a PND of TS are influenced by a complex interplay of medical, psychological, and socio-cultural factors. Addressing these determinants through patient-centered, non-directive counseling and equitable access to genetic expertise can support informed decision making.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32140"},"PeriodicalIF":2.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing With Purpose: Treatment of Bachmann-Bupp Syndrome With Eflornithine and Implications for Other Polyaminopathies.","authors":"Caleb P Bupp, Elizabeth A VanSickle, Julianne Michael, Chad R Schultz, Kelly Nguyen, Melissa Hoefer, Surender Rajasekaran, André S Bachmann","doi":"10.1002/ajmg.c.32138","DOIUrl":"https://doi.org/10.1002/ajmg.c.32138","url":null,"abstract":"<p><p>Rare diseases impact approximately 1 in 10 people worldwide, and yet, less than 5% of all rare diseases currently have an approved treatment option available. This is due to many challenges unique to rare diseases, including small, diverse patient populations, the cost of drug development that is not proportionate to the number of patients who could potentially benefit from treatment, and difficulty with clinical trial design to validate new therapeutics. As a result, drug repurposing has become an increasingly promising option for finding treatment options for rare diseases. First described in 2018, Bachmann-Bupp Syndrome (BABS) is a rare neurodevelopmental disorder that is caused by gain-of-function variants in the ornithine decarboxylase (ODC1) gene and is characterized by developmental delay, hypotonia, and alopecia. Through collaboration and the use of a unique drug repurposing strategy, the first patient identified with BABS was treated with the repurposed drug eflornithine, also known as α-difluoromethylornithine (DFMO), in just 16 months. Currently, five additional patients with BABS are being treated with DFMO. This model of drug repurposing of an FDA-approved drug for use in another indication can serve as an example of what is possible in the scope of other rare diseases, specifically in other polyaminopathies.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32138"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Cardiovascular Health Issues in Turner Syndrome: Expert Insights and Expanded Recommendations From the 2024 Guideline Development Team.","authors":"Katya de Groote, Sheetal R Patel, Kristian Havmand Mortensen, Isabel Witvrouwen, Anthonie Duijnhouwer, Nicole M Brown, Jasmine Grewal, Kathryn C Chatfield, Aaron T Dorfman, Siddharth K Prakash","doi":"10.1002/ajmg.c.32139","DOIUrl":"https://doi.org/10.1002/ajmg.c.32139","url":null,"abstract":"<p><p>Turner syndrome (TS) is frequently complicated by congenital heart disease (CHD). While left-sided lesions such as bicuspid aortic valve (BAV) and coarctation of the aorta are the most common structural heart lesions in TS, other anomalies, such as aortic arch malformations, hypoplastic left heart syndrome (HLHS), persistent left superior vena cava (LSVC), and partial anomalous pulmonary venous return (PAPVR), are also relatively frequent. Standardized mortality is increased threefold in individuals with TS compared to the general population, with cardiovascular complications, including aortic dissection, being the leading cause of death. The publication of the 2024 Clinical Practice Guidelines for TS marks an important opportunity to remind clinicians about the burden of congenital heart and vascular lesions in TS and the need for lifelong cardiovascular surveillance. In this expert panel statement, we will focus on the rationale for clinical management of CHD in TS, emphasizing TS-specific features of CHD that influence clinical decision making about therapeutic options and follow-up care.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32139"},"PeriodicalIF":2.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}