American Journal of Medical Genetics Part C: Seminars in Medical Genetics最新文献_第2页

IF 2.8 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-06-02 DOI: 10.1002/ajmg.c.32144

Kirstine Stochholm, Astrid Bruun Rasmussen, Anne Skakkebæk

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Table of Contents, Volume 199, Number 1, March 2025 目录，第199卷，第1期，2025年3月

IF 2.8 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-05-21 DOI: 10.1002/ajmg.c.32091

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Cover Image, Volume 199, Number 1, March 2025 封面图片，第199卷，第1期，2025年3月

IF 2.8 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-05-21 DOI: 10.1002/ajmg.c.32143

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Comment From the Guest Editors 客座编辑的评论。

IF 2.8 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-04-30 DOI: 10.1002/ajmg.c.32141

Melissa L. Crenshaw, Anne Skakkebæk

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A Genomic Analysis of Usher Syndrome: Population-Scale Prevalence and Therapeutic Targets. Usher综合征的基因组分析：人群规模的患病率和治疗目标。

IF 4.4 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-04-18 DOI: 10.1002/ajmg.c.32142

Shelby E Redfield, Stephanie A Mauriac, Gwenaëlle S Géléoc, A Eliot Shearer

{"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":"10.1002/ajmg.c.32142","url":null,"abstract":"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.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32142"},"PeriodicalIF":4.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353266/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Parental Decision-Making Following a Prenatal Diagnosis of Turner Syndrome: A Systematic Review. 特纳综合征产前诊断后的父母决策：系统回顾。

IF 2.8 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-04-08 DOI: 10.1002/ajmg.c.32140

Inger Lily Hjuler Dorf, Stina Lou, Anne Skakkebæk

{"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":"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.","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}

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Repurposing With Purpose: Treatment of Bachmann-Bupp Syndrome With Eflornithine and Implications for Other Polyaminopathies. 有目的的重新利用：依氟鸟氨酸治疗巴赫曼-布普综合征及其对其他多胺病的影响。

IF 4.4 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-04-01 DOI: 10.1002/ajmg.c.32138

Caleb P Bupp, Elizabeth A VanSickle, Julianne Michael, Chad R Schultz, Kelly Nguyen, Melissa Hoefer, Surender Rajasekaran, André S Bachmann

{"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":"10.1002/ajmg.c.32138","url":null,"abstract":"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.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32138"},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353620/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Management of Cardiovascular Health Issues in Turner Syndrome: Expert Insights and Expanded Recommendations From the 2024 Guideline Development Team. 特纳综合征心血管健康问题的管理：2024指南制定团队的专家见解和扩展建议

IF 2.8 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-03-26 DOI: 10.1002/ajmg.c.32139

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

{"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":"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.","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}

引用次数: 0

In Utero Therapies, the Next Frontier. 子宫内治疗，下一个前沿。

IF 2.8 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-03-24 DOI: 10.1002/ajmg.c.32135

Teodora R Kolarova, Edith Cheng

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Evaluation of Targeted Therapies Currently Available for Congenital Genetic Conditions Indexed in GeneReviews. 目前在GeneReviews中索引的先天性遗传疾病的靶向治疗的评估。

IF 2.8 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-03-18 DOI: 10.1002/ajmg.c.32137

Nathan B Adam, Anne R Amemiya, Stephanie E Wallace, Caitlin T Mahon, Ghayda M Mirzaa, Margaret P Adam

{"title":"Evaluation of Targeted Therapies Currently Available for Congenital Genetic Conditions Indexed in GeneReviews.","authors":"Nathan B Adam, Anne R Amemiya, Stephanie E Wallace, Caitlin T Mahon, Ghayda M Mirzaa, Margaret P Adam","doi":"10.1002/ajmg.c.32137","DOIUrl":"https://doi.org/10.1002/ajmg.c.32137","url":null,"abstract":"In this study, we propose a definition of targeted therapy and use GeneReviews, a peer-reviewed, online point-of-care resource for primarily constitutional (or rare congenital mosaic) genetic conditions, to compile a list of primarily heritable genetic disorders for which such targeted therapy is available. This study aims to give a high-level view of the types of targeted therapies and the proportion of congenital genetic disorders for which a targeted therapy is available. We propose that a targeted therapy is one that addresses the underlying molecular mechanism of the disorder and/or can alter the disease course (including by providing a cure in some instances) but may not be an obvious treatment option without knowledge of the patient's underlying genetic condition. For the purposes of this study, a treatment meeting one or both of these criteria was categorized as targeted. This means that the clinician might not consider the specific treatment option unless the patient was known to have the genetic diagnosis. This definition does not include therapies based on symptoms alone, which does not rely on the clinician being aware of a patient's genetic diagnosis. As most of the congenital genetic conditions in this study are rare and often diagnosed in a pediatric age group, determining efficacy for the specific use of most of the targeted therapies is not possible, although any drug or medication in the Management section of GeneReviews is approved by the Food and Drug Administration (FDA), with rare exceptions for drugs approved by the European Medicines Agency (EMA) of the European Union (EU) but not yet FDA approved. Of 790 GeneReviews chapters on primarily constitutional genetic conditions included in this study, 176 chapters representing over 255 genes meet the definition of having a targeted therapy.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32137"},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655849","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}

引用次数: 0