American Journal of Medical Genetics Part A最新文献

Perspectives on the Current and Future State of Artificial Intelligence in Medical Genetics. 人工智能在医学遗传学研究中的现状与未来展望

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-05-15 DOI: 10.1002/ajmg.a.64118

Benjamin D Solomon, Morgan Cheatham, Thales A C de Guimarães, Dat Duong, Melissa A Haendel, Tzung-Chien Hsieh, Behnam Javanmardi, Britt Johnson, Peter Krawitz, Paul Kruszka, Tim Laurent, Ni-Chung Lee, Kirsty McWalter, Michel Michaelides, Klaus Mohnike, Nikolas Pontikos, Maria J Guillen Sacoto, Yousif J Shwetar, Vincent D Ustach, Rebekah L Waikel, William Woof

{"title":"Perspectives on the Current and Future State of Artificial Intelligence in Medical Genetics.","authors":"Benjamin D Solomon, Morgan Cheatham, Thales A C de Guimarães, Dat Duong, Melissa A Haendel, Tzung-Chien Hsieh, Behnam Javanmardi, Britt Johnson, Peter Krawitz, Paul Kruszka, Tim Laurent, Ni-Chung Lee, Kirsty McWalter, Michel Michaelides, Klaus Mohnike, Nikolas Pontikos, Maria J Guillen Sacoto, Yousif J Shwetar, Vincent D Ustach, Rebekah L Waikel, William Woof","doi":"10.1002/ajmg.a.64118","DOIUrl":"https://doi.org/10.1002/ajmg.a.64118","url":null,"abstract":"Artificial intelligence (AI) is rapidly transforming numerous aspects of daily life, including clinical practice and biomedical research. In light of this rapid transformation, and in the context of medical genetics, we assembled a group of leaders in the field to respond to the question about how AI is affecting, and especially how AI will affect, medical genetics. The authors who contributed to this collection of essays intentionally represent different areas of expertise, career stages, and geographies, and include diverse types of clinicians, computer scientists, and researchers. The individual pieces cover a wide range of areas related to medical genetics; we expect that these pieces may provide helpful windows into the ways in which AI is being actively studied, used, and considered in medical genetics.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64118"},"PeriodicalIF":1.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to "Novel CHRNA3 Variants Identified in a Patient With Bladder Dysfunction, Dysautonomia, and Gastrointestinal Dysmotility". 更正“在膀胱功能障碍、自主神经障碍和胃肠运动障碍患者中发现的新型CHRNA3变异”。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-05-15 DOI: 10.1002/ajmg.a.64114

引用次数: 0

Characteristics of Early Language Development in Children With Williams Syndrome. 威廉姆斯综合征儿童早期语言发展的特点。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-05-15 DOI: 10.1002/ajmg.a.64103

Dan Yao, Wei-Jun Chen, Fang-Fang Li, Ji-Yang Shen, Chai Ji

{"title":"Characteristics of Early Language Development in Children With Williams Syndrome.","authors":"Dan Yao, Wei-Jun Chen, Fang-Fang Li, Ji-Yang Shen, Chai Ji","doi":"10.1002/ajmg.a.64103","DOIUrl":"https://doi.org/10.1002/ajmg.a.64103","url":null,"abstract":"Williams Syndrome (WS) is a rare neurodevelopmental disorder characterized by dissonance in cognition and language. The purpose of this study was to investigate the characteristics of early language development in WS children. Seventeen children, aged 2-5 years, diagnosed with WS in the outpatient department of child healthcare in our hospital from December 2020 to June 2023, were included in this study. In the same period, 39 children with global developmental delay (GDD) diagnosed in the outpatient department of child healthcare in our hospital were included as the control group. All children underwent cognitive and language development assessments. The language development characteristics of WS children and the differences between WS children and children with total developmental delay were observed and analyzed. WS children had weaker language comprehension ability but significantly stronger expression ability than GDD children. Intra-group comparison found that most children in the WS group expressed better than they understood; the level of expression is relatively higher than the level of comprehension. While most children in the GDD group understood better than they expressed, the level of comprehension is relatively higher than the level of expression. In addition, the language imitation ability of WS children is significantly better than that of GDD children. Our findings suggest the outstanding feature of verbal ability is expression ability and language imitation ability of WS children; the comprehension ability is still weak. These findings can help us explore intervention methods that enable WS children to reach their full potential, so as to provide guidance for the education and rehabilitation strategies for WS patients.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64103"},"PeriodicalIF":1.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parental Communication With Their Children About Cancer Risk and DTC. 父母与子女关于癌症风险和DTC的沟通。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-05-13 DOI: 10.1002/ajmg.a.64115

Marcelo M Sleiman, Talia Zamir, Beth N Peshkin, Jada G Hamilton, Mingqian Liu, Mary Rose Yockel, Benjamin Wilfond, Lainie Friedman Ross, Jamie Brower, Hannah Ovadia, Rosalba Sacca, Beth Tarini, Susan M Domchek, Claudine Isaacs, Kenneth P Tercyak

{"title":"Parental Communication With Their Children About Cancer Risk and DTC.","authors":"Marcelo M Sleiman, Talia Zamir, Beth N Peshkin, Jada G Hamilton, Mingqian Liu, Mary Rose Yockel, Benjamin Wilfond, Lainie Friedman Ross, Jamie Brower, Hannah Ovadia, Rosalba Sacca, Beth Tarini, Susan M Domchek, Claudine Isaacs, Kenneth P Tercyak","doi":"10.1002/ajmg.a.64115","DOIUrl":"https://doi.org/10.1002/ajmg.a.64115","url":null,"abstract":"Cascade genetic testing for cancer risk can influence relatives' health outcomes, as they may benefit from risk reduction and screening. However, clinical guidelines discourage predictive genetic testing in childhood-including direct-to-consumer (DTC) testing. This study examined high-risk parents' preparation of their children (primarily adolescents and young adults) for cascade genetic testing for adult-onset inherited cancers. Surveys were completed by N = 126 parents with pathogenic variants predisposing to adult-onset inherited cancers included on DTC testing panels. A total of 81% of children were aware of their parents' hereditary cancer predisposition and 62% of parents had discussed their children's participation in cancer genetic testing. Potential risks of DTC testing identified by parents included lack of engagement with clinicians; potential benefits were its usefulness for child/family health and convenience. Parents with older children (B = 0.07, p = < 0.001), greater confidence in using genetic information (B = 0.02, p < 0.05), and who held more favorable opinions about pediatric genetic testing (B = 0.02, p < 0.01) were more likely to make their children aware of their familial cancer risk and discuss cascade testing. Most high-risk parents discuss hereditary cancer and testing options with their older children. Research is needed to enrich understanding of healthcare professionals' roles in navigating the implications of cascade genetic testing choices within the family, including DTC testing.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64115"},"PeriodicalIF":1.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Absence of Neurodevelopmental Impairment in an Individual With KCNN3-Related Zimmermann Laband Syndrome. kcnn3相关齐默尔曼-拉班综合征患者无神经发育障碍

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-05-13 DOI: 10.1002/ajmg.a.64113

Zeynep Esener, Gül Ünsel-Bolat

{"title":"Absence of Neurodevelopmental Impairment in an Individual With KCNN3-Related Zimmermann Laband Syndrome.","authors":"Zeynep Esener, Gül Ünsel-Bolat","doi":"10.1002/ajmg.a.64113","DOIUrl":"https://doi.org/10.1002/ajmg.a.64113","url":null,"abstract":"Zimmermann-Laband syndrome (ZLS) is a rare group of potassium channelopathies presenting with characteristic facial findings, gingival hyperplasia, hypertrichosis, hypoplasia of phalanges and nails, neurodevelopmental disorders, and intellectual disability. KCNN3 related ZLS3 has been recently recognized. We detected a de novo heterozygous c.1606G>A variant in the KCNN3 gene using clinical exome sequencing. Our patient presented facial dysmorphism, ptosis and strabismus, pectus excavatum, hypertrichosis of the trunk and limbs, tapering fingers, hypoplastic nails, and gingival hyperplasia but no neurodevelopmental disorder or behavioral problems. To the best of our knowledge, our case is the ninth case of ZLS3 syndrome in the literature. We report a further case of ZLS3 without intellectual disability who, in addition, had a normal development as an infant. Previous cases of monozygotic twins were reported carrying the same variant in the KCNN3 gene. Twin sisters carrying the same variant in our study were reported to have developmental delay, but their intellectual level is normal in adulthood. We suggest KCNN3 related ZLS3 may not be associated with any neurodevelopmental disorder; that is an important issue for genetic counseling.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64113"},"PeriodicalIF":1.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dentofacial Malocclusion in Neurofibromatosis 1 in Finland. 芬兰神经纤维瘤病的牙面错颌1。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-05-13 DOI: 10.1002/ajmg.a.64110

Vivian Reinhold, Mikko Valtanen, Kari Auranen, Stina Syrjänen, Sirkku Peltonen, Juha Peltonen, Roope A Kallionpää

{"title":"Dentofacial Malocclusion in Neurofibromatosis 1 in Finland.","authors":"Vivian Reinhold, Mikko Valtanen, Kari Auranen, Stina Syrjänen, Sirkku Peltonen, Juha Peltonen, Roope A Kallionpää","doi":"10.1002/ajmg.a.64110","DOIUrl":"https://doi.org/10.1002/ajmg.a.64110","url":null,"abstract":"Neurofibromatosis 1 (NF1) is an inherited disease that can be accompanied by oral health problems such as caries, periodontitis, and tumors affecting the oral cavity. Also, different maxillary and mandibular malformations are associated with NF1. In this retrospective register-based study, we evaluated hospital visits related to dentofacial malocclusion in 1349 individuals with NF1, 13,870 matched controls and 1894 non-NF1 siblings followed up over 1998-2014 using the Finnish Care Register for Health Care that covers information on inpatient care and specialist outpatient care. Hazard ratios (HRs) and their 95% confidence intervals (CI) were estimated with the Cox proportional hazards model. Individuals with NF1 had a higher hazard for hospital visits related to embedded and impacted teeth (HR 2.1, 95% CI 1.2-3.5), disorders of tooth development and eruption (HR 3.7, 95% CI 1.9-7.1), and dentofacial anomalies (HR 2.7, 95% CI 1.9-3.8) such as anomalies in dental arch relationship (HR 4.8, 95% CI 2.9-7.9) and anomalies of jaw-cranial base relationship (HR 2.2, 95% CI 1.1-4.3) compared with controls. Plexiform neurofibromas did not markedly affect the estimates. Early detection of jaw and dental alterations, which may be linked to previously identified cephalometric features of NF1, is important for preventing occlusal defects, maintaining oral hygiene, and preserving quality of life.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64110"},"PeriodicalIF":1.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trigeminal Neuralgia in a 12-Month-Old Boy With Dandy-Walker Malformation and Homozygous Pathogenic TOPORS Variant. 三叉神经痛1例12月大婴儿伴Dandy-Walker畸形和纯合子致病性TOPORS变异。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-05-13 DOI: 10.1002/ajmg.a.64117

K N Lob, W D Brown

{"title":"Trigeminal Neuralgia in a 12-Month-Old Boy With Dandy-Walker Malformation and Homozygous Pathogenic TOPORS Variant.","authors":"K N Lob, W D Brown","doi":"10.1002/ajmg.a.64117","DOIUrl":"https://doi.org/10.1002/ajmg.a.64117","url":null,"abstract":"A 12-month-old boy with a Dandy-Walker malformation (DWM) presented with a 2-month history of lip chewing and face rubbing such that disfiguring ulcerations were present on his lips and right eye. The persistently frequent but intermittent behaviors during wakefulness lasted minutes at a time numerous times each hour of the day and were associated with pronounced irritability relieved only with sleep. Analgesics were unhelpful. Carbamazepine at anticonvulsant doses was deployed for a presumptive diagnosis of trigeminal neuralgia (TN), which not only resulted in an estimated 90% reduction of the self-injurious behaviors after a month, but also enabled the lip and right eye lesions to completely heal over the next several months. Genetic testing (exome sequencing [ES]) demonstrated a homozygous pathogenic variant in the TOPORS gene (c.29 C>A, p.P10Q, # OMIM 609507). We review the history of TN and Dandy-Walker syndrome (DWS) and speculate on their relationship in this patient, the youngest such reported incidence of TN in the literature while adding additional clinical features to the continuum of TOPORS phenotypes.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64117"},"PeriodicalIF":1.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical and Genetic Landscape of IGHMBP2-Related Disorders: From Novel Variants to Phenotypic Insights. ighmbp2相关疾病的临床和遗传景观：从新的变异到表型的见解。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-05-12 DOI: 10.1002/ajmg.a.64116

Tinatin Tkemaladze, Kakha Bregvadze, Luka Abashishvili, Gocha Chikvinidze, Angelica Maria Delgado Vega, Fizza Akbar, Sara Khan, Salman Kirmani

引用次数: 0

Case Report: Unusual Neurological Features of Leigh Syndrome due to m.8993T>G Pathogenic Variant in the MT-ATP6 Gene. 病例报告：MT-ATP6基因m.8993T>G致病性变异引起Leigh综合征的异常神经学特征

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-05-09 DOI: 10.1002/ajmg.a.64112

Ramya Treitel, Julie McLaughlin, Marta Frigeni

{"title":"Case Report: Unusual Neurological Features of Leigh Syndrome due to m.8993T>G Pathogenic Variant in the MT-ATP6 Gene.","authors":"Ramya Treitel, Julie McLaughlin, Marta Frigeni","doi":"10.1002/ajmg.a.64112","DOIUrl":"https://doi.org/10.1002/ajmg.a.64112","url":null,"abstract":"The MT-ATP6 gene m.8993T>G pathogenic variant has been associated with Leigh syndrome, especially in patients exhibiting a high degree of heteroplasmy. Although patients may present with a wide phenotypic spectrum, characteristic findings include bilateral, symmetric hyperintensities in the basal ganglia and brainstem on brain MRI, particularly on T2-weighted and fluid-attenuated inversion recovery sequences. Additionally, the biochemical phenotype associated with this pathogenic variant often mimics that of multiple carboxylase deficiency and proximal urea cycle disorders. This report describes a male infant with an atypical neurological presentation of Leigh syndrome. At 2 months of age, he presented with status epilepticus of left temporal origin that was refractory to treatment. Initial brain MRI revealed a large region of non-enhancing signal abnormality in the left temporal lobe, raising concern for an infectious etiology. However, biochemical testing revealed hypocitrullinemia, elevated 3-hydroxyisovalerylcarnitine, elevated propionylcarnitine, and urinary excretion of lactate and pyruvate, prompting further investigation for MT-ATP6 mitochondrial disease. Mitochondrial DNA analysis confirmed the presence of a homoplasmic m.8993T>G pathogenic variant in the MT-ATP6 gene. Despite treatment with citrulline and high-dose biotin, the patient died 5 weeks later due to cardiorespiratory failure following a severe respiratory infection. Retrospective review of his newborn screening revealed two screens positive for low citrulline that were ultimately cleared on a third screen, delaying the diagnosis. This case underscores the importance of considering MT-ATP6 mitochondrial disease in the differential diagnosis of patients presenting with atypical neurological symptoms and biochemical abnormalities. It also highlights the value of newborn screening in identifying potential mitochondrial disorders, where early diagnosis and timely intervention may improve outcomes, even in severe cases.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64112"},"PeriodicalIF":1.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DHX16-Associated Neuromuscular Oculoauditory Syndrome: A Novel Case. dhx16相关神经肌肉眼听综合征：一个新病例。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-05-06 DOI: 10.1002/ajmg.a.64083

Sloane Clay, Alejandro Leon, Luke Wall, Regina M Zambrano

{"title":"DHX16-Associated Neuromuscular Oculoauditory Syndrome: A Novel Case.","authors":"Sloane Clay, Alejandro Leon, Luke Wall, Regina M Zambrano","doi":"10.1002/ajmg.a.64083","DOIUrl":"https://doi.org/10.1002/ajmg.a.64083","url":null,"abstract":"DHX16, a member of the DexD/H-box RNA helicase family, facilitates ATP-dependent unwinding of RNA secondary structures. Pathogenic variants cause poor functioning of the spliceosome complex leading to intron retention in gene transcripts. Clinically, it is associated with neuromuscular oculoauditory syndrome (MIM #618733). To date, there are nine published cases. We report a tenth case: a 3-year-old female, initially presented at 7 months of age, with mild developmental delay, ocular anomalies, dysmorphia, and increased infections. An inherited retinal disorder panel identified nondiagnostic variants of uncertain significance. Trio exome sequencing revealed a de novo Likely Pathogenic DHX16 variant, c.692G>C; p.R231P. Published cases of DHX16-related disorders report developmental delay/intellectual disability, seizures, myopathy, retinal anomalies, myopia, nystagmus, and hearing loss. No published variants to date are located upstream of the start of the helicase domain, and little is known about upstream domains. In silico analysis demonstrates evidence of pathogenicity, while Missense3D modeling demonstrates no structural damage to the protein. These findings are consistent with current literature, suggesting a mechanism of pathogenicity that is difficult to assess via modeling. This case illustrates a DHX16 variant in an unknown domain displaying a mild phenotype.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64083"},"PeriodicalIF":1.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0