American Journal of Medical Genetics Part C: Seminars in Medical Genetics最新文献_第4页

Table of Contents, Volume 199, Number 2, June 2025 目录，第199卷，第2号，2025年6月

IF 4.4 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-11-14 DOI: 10.1002/ajmg.c.32092

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Cover Image, Volume 199, Number 2, June 2025 封面图片，第199卷第2期，2025年6月

IF 4.4 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-11-14 DOI: 10.1002/ajmg.c.32162

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

IF 4.4 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-10-30 DOI: 10.1002/ajmg.c.32157

Melissa Crenshaw, Anne Skakkebæk

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Bone Health and Pubertal Induction in Turner Syndrome: The Possibility of Earlier Transdermal Lower-Dose Estradiol Therapy for Healthy Bone Density and Quality 特纳综合征的骨健康和青春期诱导：早期经皮低剂量雌二醇治疗健康骨密度和质量的可能性。

IF 4.4 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-10-21 DOI: 10.1002/ajmg.c.32155

Yukihiro Hasegawa, Kento Ikegawa, Takeshi Munenaga, Tomoyo Itonaga, Marie Mitani-Konno, Masanobu Kawai, Naoko Amano

{"title":"Bone Health and Pubertal Induction in Turner Syndrome: The Possibility of Earlier Transdermal Lower-Dose Estradiol Therapy for Healthy Bone Density and Quality","authors":"Yukihiro Hasegawa, Kento Ikegawa, Takeshi Munenaga, Tomoyo Itonaga, Marie Mitani-Konno, Masanobu Kawai, Naoko Amano","doi":"10.1002/ajmg.c.32155","DOIUrl":"10.1002/ajmg.c.32155","url":null,"abstract":"The effect of estrogen deficiency on bone health in Turner syndrome (TS) may be a concern even before adulthood. Previous guidelines have discussed hormone replacement therapy (HRT) in children with TS. However, some practical issues related to puberty induction in TS require clarification, such as how to implement HRT to achieve adequate bone health. It is generally assumed that earlier initiation of HRT will result in better bone health in young adults with TS and estrogen deficiency. The present study reviews pubertal development, bone health, and current pubertal induction therapies in TS, with a particular focus on patients without endogenous estrogen production. Current guidelines recommend using transdermal estradiol patches starting at the age of 11–12 years if necessary to mimic the gradual increase in circulating, physiological estradiol. Theoretically, earlier therapy combined with forecasting estrogen deficiency on the basis of increased FSH may allow a closer approximation to endogenous estradiol secretion in patients with TS without spontaneous puberty. This approach may lead to better long-term outcomes, such as the acquisition of normal bone mineral density. Further research is needed to assess how the achievement of normal bone density and bone quality relates to the timing of HRT in children and young adults with TS. The resulting improvements in transdermal estradiol therapy may help patients with TS achieve optimal bone health.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"199 2","pages":"107-115"},"PeriodicalIF":4.4,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342650","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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Correction to "The Rise of the Genetic Counseling Profession in China". 更正“遗传咨询行业在中国的兴起”。

IF 4.4 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-10-21 DOI: 10.1002/ajmg.c.32154

引用次数: 0

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 4.4 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-09-01 Epub 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":"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":"143-150"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","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}

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Treatment of PDGFRB -Related Penttinen Syndrome With Imatinib in a Young Child. 伊马替尼治疗幼儿pdgfrb相关Penttinen综合征

IF 4.4 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-09-01 Epub Date: 2025-07-31 DOI: 10.1002/ajmg.c.32148

Molly McPheron, Katelyn Burns, Tara L Wenger

{"title":"Treatment of PDGFRB -Related Penttinen Syndrome With Imatinib in a Young Child.","authors":"Molly McPheron, Katelyn Burns, Tara L Wenger","doi":"10.1002/ajmg.c.32148","DOIUrl":"10.1002/ajmg.c.32148","url":null,"abstract":"PDGFRB-related Penttinen syndrome is characterized by progressive progeroid features, acroosteolysis, and development of aneurysms, structural anomalies of the posterior fossa, variable myofibromatosis, and overgrowth. PDGFRB-related disorders, including Penttinen syndrome, Kosaki syndrome, and infantile myofibromatosis, have been successfully treated using imatinib. Here, we report a child diagnosed in infancy who initiated imatinib monotherapy at 8 months of age and has continued treatment for 4 years. At the time of diagnosis, he was known to have structural anomalies of the posterior fossa, sparse hair, joint stiffness, myofibromatosis, thin and fragile skin, decreased subcutaneous fat, and prominent vasculature. Imatinib has been well tolerated without apparent side effects. Within weeks to months after initiating imatinib, he grew thick curly hair, and the texture of his skin and joint stiffness had marked improvement. Over the past 4 years, he has not developed acroosteolysis and continues to have normal hair growth. Surveillance MRA has not identified aneurysms or vessel ectasia. Height decreased from 90th to 75th percentile. He has mild developmental delays and is awaiting formal evaluation for autism spectrum disorder. Overall, early imatinib treatment has been successful in ameliorating and preventing the development of some features of Penttinen syndrome.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"176-182"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752081","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

Prenatal Delivery of Enzyme Replacement Therapy to Fetuses Affected by Early-Onset Lysosomal Storage Diseases. 早发性溶酶体贮积病胎儿的产前酶替代治疗。

IF 4.4 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-09-01 Epub Date: 2025-01-31 DOI: 10.1002/ajmg.c.32132

Beltran Borges, Emma Canepa, Irene J Chang, Akos Herzeg, Billie Lianoglou, Priya S Kishnani, Paul Harmatz, Tippi C MacKenzie, Jennifer L Cohen

{"title":"Prenatal Delivery of Enzyme Replacement Therapy to Fetuses Affected by Early-Onset Lysosomal Storage Diseases.","authors":"Beltran Borges, Emma Canepa, Irene J Chang, Akos Herzeg, Billie Lianoglou, Priya S Kishnani, Paul Harmatz, Tippi C MacKenzie, Jennifer L Cohen","doi":"10.1002/ajmg.c.32132","DOIUrl":"10.1002/ajmg.c.32132","url":null,"abstract":"The expansion of prenatal genetic screening and diagnosis warrants the evaluation of approved postnatal therapies that may be safely and feasibly translated to prenatal administration to a fetus affected by monogenic disease. For lysosomal storage diseases (LSDs), enzyme replacement therapy (ERT) often represents the main therapeutic approach. In utero enzyme replacement therapy (IUERT) has several potential benefits compared to postnatal therapy, such as: (1) delivering enzyme before the onset of irreversible organ damage; (2) developing tolerance toward the recombinant enzyme; and (3) targeting the central nervous system through a more permeable blood-brain barrier. In this review, we examine the general and disease-specific rationale for IUERT, and provide an overview of the main elements of our current clinical trial for the prenatal treatment of early-onset lysosomal storage diseases. Trial Registration: IUERT clinical trial: NCT04532047; Alpha thalassemia clinical trial: NCT02986698.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"203-217"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073406","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

Genomics Review of Selective RET Inhibitors Sensitivity in Thyroid Cancer Clinical Trials. 甲状腺癌临床试验中选择性RET抑制剂敏感性的基因组学综述。

IF 4.4 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-09-01 Epub Date: 2025-01-04 DOI: 10.1002/ajmg.c.32127

Sara Gil-Bernabé, Lucía García-DeLaFuente, Alejandro García-Álvarez, Ginesa García-Rostán, Jaume Capdevila, Jorge Hernando

{"title":"Genomics Review of Selective RET Inhibitors Sensitivity in Thyroid Cancer Clinical Trials.","authors":"Sara Gil-Bernabé, Lucía García-DeLaFuente, Alejandro García-Álvarez, Ginesa García-Rostán, Jaume Capdevila, Jorge Hernando","doi":"10.1002/ajmg.c.32127","DOIUrl":"10.1002/ajmg.c.32127","url":null,"abstract":"RET gene is a driver of thyroid cancer (TC) tumorigenesis. The incidence of TC has increased worldwide in the last few decades, both in medullary and follicular-derived subtypes. Several drugs, including multikinase and selective inhibitors, have been explored. Selpercatinib and pralsetinib are selective RET inhibitors that have shown clear clinical benefits for patients in the LIBRETTO and ARROW trials, respectively. Currently, their development and application in clinical practice are ongoing. However, its efficacy in different RET pathogenic variants has not yet been well established. Although selpercatinib and pralsetinib achieved a high ORR, no data are available regarding the differences in tumor responses of both TC groups according to RET pathogenic variants. Clinical trials and literature have analyzed the efficacy of selective RET inhibitors with a special interest in the most common variants. A review of LIBRETTO and ARROW trials was made regarding the change in tumor size depending on the pathogenic variants. M918T pathogenic variant resulted in a higher complete response rate. Patients who underwent fusion had the highest ORR (objective response rate). MKi-treated patients did not exhibit significant differences from untreated patients. Different RET pathogenic variants are not biomarkers of RETi response in TC. Selpercatinib showed a tendency to achieve a complete response. All patients with RET pathogenic variants should receive treatment with selpercatinib or pralsetinib at any moment of the therapeutic schedule owing to off-target inhibition and toxicity. Therefore, new targets for drug sensitivity and resistance should be explored.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"228-238"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926238","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

Targeted Medical Therapies for Vascular Anomalies: A Clinical Review. 血管异常的靶向药物治疗：临床综述

IF 4.4 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-09-01 Epub Date: 2025-11-27 DOI: 10.1002/ajmgc.70000

Whitney Eng

{"title":"Targeted Medical Therapies for Vascular Anomalies: A Clinical Review.","authors":"Whitney Eng","doi":"10.1002/ajmgc.70000","DOIUrl":"10.1002/ajmgc.70000","url":null,"abstract":"Vascular anomalies represent a broad spectrum of disorders characterized by aberrant blood or lymphatic vessel development, which can lead to complex clinical phenotypes. Historically, vascular anomalies were classified solely on the basis of their clinical and histopathologic features. However, the last two decades have witnessed significant advances in our understanding of the genetic basis of these lesions. It is now recognized that many vascular anomalies arise from somatic pathogenic variants in key growth signaling pathways, including the PI3K-AKT-mTOR and RAS-MAPK pathways. These insights have catalyzed the development of targeted therapies designed to address the molecular underpinnings of disease. mTOR inhibitors, originally developed and widely used as anticancer agents, have also demonstrated significant efficacy in improving outcomes for patients with low-flow vascular malformations such as lymphatic malformations and venous malformations. Similarly, MEK inhibitors and other oncology drugs are being repurposed as promising therapeutic options for complex lymphatic anomalies and arteriovenous malformations, conditions that historically have had limited medical therapeutic options. Clinical trials for vascular anomalies are emerging, but questions remain about how to best measure response in these patients, as well as the optimal duration of treatment. This case-based review explores recent developments in precision medicine for vascular anomalies, highlighting a paradigm shift in the management of these complex and often therapeutically challenging disorders.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"161-175"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627622","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