Clinical Genetics最新文献

Mainstreaming Cancer Genomic Testing: A Scoping Review of the Acceptability, Efficacy, and Impact. 癌症基因组检测主流化：癌症基因组检测主流化：可接受性、有效性和影响的范围审查》。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-01 Epub Date: 2024-11-27 DOI: 10.1111/cge.14660

Jennifer Berkman, Emily DeBortoli, Julia Steinberg, Vivienne Milch, Tatiane Yanes, Aideen McInerney-Leo

{"title":"Mainstreaming Cancer Genomic Testing: A Scoping Review of the Acceptability, Efficacy, and Impact.","authors":"Jennifer Berkman, Emily DeBortoli, Julia Steinberg, Vivienne Milch, Tatiane Yanes, Aideen McInerney-Leo","doi":"10.1111/cge.14660","DOIUrl":"10.1111/cge.14660","url":null,"abstract":"Finite clinical genetics services combined with expanding genomic testing have driven development of mainstreaming models-of-care for genomic testing: specifically genetic counselor embedded (GEM) and upskilled-clinician (UPC) models. To determine feasibility, acceptability, and health economic impact in cancer mainstreaming settings we conducted a scoping review of the literature. A comprehensive PubMed search identified relevant manuscripts, published in English between 2013 and 2023. Of 156 identified articles, 37 proceeded to full review, encompassing five cancer types. In both models-of-care, testing uptake was > 90% and referral/testing rates increased 1.2-6.7-fold. Time from diagnosis to result disclosure decreased 1.5-6-fold and pathogenic variant detection rates were ≥ 10%. GEM model studies evaluated neither cost-effectiveness nor physician/patient outcomes. UPC models were economically viable, primarily through reducing genetics-related appointments. Physicians found the UPC model workload acceptable and reported improvements in knowledge and confidence. Patient distress in the UPC model was low overall and comparable to standard-of-care. Patients' acceptance and satisfaction/decisional satisfaction were high, and continuity-of-care was appreciated. Mainstreaming cancer genomic testing is feasible and beneficial to patients, physicians, and healthcare systems. More studies are needed to capture GEM model impacts and to compare GEM with UPC models. Further detail of allied health and nursing support for the UPC model is also required.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":"123-135"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726575","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

ME2 Deficiency Is Associated With Recessive Neurodevelopmental Disorder. ME2缺陷与隐性神经发育障碍有关

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-01 Epub Date: 2024-10-14 DOI: 10.1111/cge.14632

Naif A M Almontashiri, Essa Alharby, Mohammed Saleh, Mohamed Abu-Farha, Ali Alasmari, Marinella Gebbia, Charlotte Hiesl, Roy W A Peake, Sami Samir Amr, Eckhard Boles, Frederick P Roth, Jehad Abubaker

{"title":"ME2 Deficiency Is Associated With Recessive Neurodevelopmental Disorder.","authors":"Naif A M Almontashiri, Essa Alharby, Mohammed Saleh, Mohamed Abu-Farha, Ali Alasmari, Marinella Gebbia, Charlotte Hiesl, Roy W A Peake, Sami Samir Amr, Eckhard Boles, Frederick P Roth, Jehad Abubaker","doi":"10.1111/cge.14632","DOIUrl":"10.1111/cge.14632","url":null,"abstract":"Malate is an important dicarboxylic acid produced from fumarate in the tricarboxylic acid cycle. Deficiencies of fumarate hydrolase (FH) and malate dehydrogenase (MDH), responsible for malate formation and metabolism, respectively, are known to cause recessive forms of neurodevelopmental disorders (NDDs). The malic enzyme isoforms, malic enzyme 1 (ME1) and 2 (ME2), are required for the conversion of malate to pyruvate. To date, there have been no reports linking deficiency of either malic enzyme isoforms to any Mendelian disease in humans. We report a patient presenting with NDD, subtle dysmorphic features, resolved dilated cardiomyopathy, and mild blood lactate elevation. Whole exome sequencing (WES) revealed a homozygous frameshift variant (c.1379_1380delTT, p.Phe460fs*22) in the malic enzyme 2 (ME2) gene resulting in truncated and unstable ME2 protein in vitro. Subsequent deletion of the yeast ortholog of human ME2 (hME2) resulted in growth arrest, which was rescued by overexpression of hME2, strongly supporting an important role of ME2 in mitochondrial function. Our results also support the pathogenicity and candidacy of the ME2 gene and variant in association with NDD. To our knowledge, this is the first report of a Mendelian human disease resulting from a biallelic variant in the ME encoding gene. Future studies are warranted to confirm ME2-associated recessive NDD.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":"201-207"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459581","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

A Strong Candidate Gene for Nonsyndromic Intellectual Disability Phenotype: SGSM3. 非综合症智障表型的强候选基因：SGSM3。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-01 Epub Date: 2024-10-10 DOI: 10.1111/cge.14631

Ayberk Turkyilmaz, Kubra Adanur Saglam, Mustafa Yilmaz, Alper Han Cebi

{"title":"A Strong Candidate Gene for Nonsyndromic Intellectual Disability Phenotype: SGSM3.","authors":"Ayberk Turkyilmaz, Kubra Adanur Saglam, Mustafa Yilmaz, Alper Han Cebi","doi":"10.1111/cge.14631","DOIUrl":"10.1111/cge.14631","url":null,"abstract":"SGSM proteins are small modulator proteins interacting with proteins in the RAS signaling pathway. Studies with mouse and human tissues indicated that SGSM genes were highly expressed in the brain and could be expressed at different levels at different stages of development in fetal and adult brain tissue. It was first reported by Birnbaum et al. that the SGSM3 gene might be associated with a Mendelian inherited disease in families of Ashkenazi Jews with clinical manifestations of intellectual disability (ID). In this study, a novel homozygous stop-gain (NM_015705.6: c.1576C>T: p.(Arg526Ter)) variation was detected in the SGSM3 gene in two siblings with short stature and ID findings. The report of two cases with bi-allelic LOF variants in the SGSM3 gene from different populations with similar clinical manifestations strengthens the potential of this gene as a candidate gene for the nonsyndromic ID phenotype. Functional studies are required to investigate the signaling pathways affected by SGSM3 gene variations to produce the ID phenotype and their effect on the functioning of neurons.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":"196-200"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399597","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

Biallelic PIGM Coding Variant Causes Intractable Epilepsy and Intellectual Disability Without Thrombotic Events. 双倍拷贝 PIGM 编码变异导致难治性癫痫和智力障碍，但无血栓事件。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-01 Epub Date: 2024-10-19 DOI: 10.1111/cge.14629

Gali Heimer, Ben Pode-Shakked, Dina Marek-Yagel, Helly Vernitsky, Michal Tzadok, Ortal Barel, Eran Eyal, Bruria Ben-Zeev, Gil Atzmon, Yair Anikster

{"title":"Biallelic PIGM Coding Variant Causes Intractable Epilepsy and Intellectual Disability Without Thrombotic Events.","authors":"Gali Heimer, Ben Pode-Shakked, Dina Marek-Yagel, Helly Vernitsky, Michal Tzadok, Ortal Barel, Eran Eyal, Bruria Ben-Zeev, Gil Atzmon, Yair Anikster","doi":"10.1111/cge.14629","DOIUrl":"10.1111/cge.14629","url":null,"abstract":"During the past two decades, an emerging group of genes coding for proteins involved in glycosylphosphatidylinositol (GPI) anchor biosynthesis are being implicated in early-infantile epileptic encephalopathy. Amongst these, a hypomorphic promoter mutation in the mannosyltransferase-encoding PIGM gene was described in seven patients to date, exhibiting intractable absence epilepsy, portal and cerebral vein thrombosis and intellectual disability (ID). We describe here three siblings exhibiting intractable epilepsy and ID, found to harbor a homozygous c.224G>A p.(Arg75His) missense variant in PIGM, which segregated with the disease in the family. The variant is evolutionary conserved, extremely rare in general population databases and predicted to be deleterious. Structural modeling of the PIGM protein and the p.(Arg75His) variant indicates that it is located in a short luminal region of the protein, predicted to be hydrophilic. Functional prediction suggests that the entire local region is sensitive to mutations, with the p.(Arg75His) variant in particular. This is the first report of a PIGM coding variant, and the second variant altogether to be described affecting this gene. This phenotype differs from that of patients with the shared PIGM promoter mutation by lack of thrombotic events and no decrease in PIGM cDNA levels or CD59 expression on red blood cells.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":"179-187"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459579","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

Genetic Variants Supporting the Diagnosis of Primary Ciliary Dyskinesia in Japan. 日本支持原发性睫状肌运动障碍诊断的基因变异。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-01 Epub Date: 2024-10-27 DOI: 10.1111/cge.14640

Minako Hijikata, Kozo Morimoto, Masashi Ito, Keiko Wakabayashi, Akiko Miyabayashi, Hiroyuki Yamada, Naoto Keicho

{"title":"Genetic Variants Supporting the Diagnosis of Primary Ciliary Dyskinesia in Japan.","authors":"Minako Hijikata, Kozo Morimoto, Masashi Ito, Keiko Wakabayashi, Akiko Miyabayashi, Hiroyuki Yamada, Naoto Keicho","doi":"10.1111/cge.14640","DOIUrl":"10.1111/cge.14640","url":null,"abstract":"Primary ciliary dyskinesia (PCD; OMIM 244400) is a rare genetic disorder affecting motile cilia and is characterized by impaired mucociliary clearance in the airway epithelium that leads to chronic oto-sinopulmonary manifestations. To date, over 50 PCD-causing genes have been identified, with these genes and their variants varying globally across populations. We performed targeted resequencing of 42 PCD-causative genes in 150 Japanese patients suspected of having PCD and identified pathogenic or likely pathogenic variants in 51 patients. Among these, 24 patients exhibited a homozygous deletion of DRC1 exons 1-4, the most common cause of PCD in Japan. The allele frequency of this deletion was estimated at 0.0034 (95% CI: 0.0025-0.0044), based on bioinformatic analysis of 7906 whole-genome sequences from the general Japanese population. Additionally, RNA sequencing of nasal samples supplemented in silico variant predictions, aiding in the identification of causative variants. Considering potential ethnic differences, it is essential to accumulate global data on these variants and their functional impacts.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":"219-223"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496292","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

Identification of a Rare Branch Point Variant in the SMS Gene in a Large Family With a Severe Form of Snyder-Robinson Syndrome. 在一个患有严重斯奈德-罗宾逊综合征的大家庭中发现 SMS 基因的罕见分支点变异。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-01 Epub Date: 2024-11-10 DOI: 10.1111/cge.14643

Antoine Civit, Nathalie Ronce, Benjamin Cogné, Thomas Besnard, David Laurenceau, Catherine Hubert, Marie-Pierre Moizard, Paul Gueguen, Annick Toutain, Marie-Laure Vuillaume

引用次数: 0

A Novel Compound Heterozygous Genotype of the WDR73 Gene Associated With a Psychomotor Retardation Syndrome Without Cerebellar Atrophy and Other CNS Structural Abnormalities. 一种新的 WDR73 基因复合杂合子基因型与精神运动发育迟缓综合征有关，但不伴有小脑萎缩和其他中枢神经系统结构异常。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-01 Epub Date: 2024-11-12 DOI: 10.1111/cge.14645

Enrique Nogueira, Beatriz Del Olmo, Lara Babín, Génesis Vizuete, Concepción Lobo, Cecilia González

引用次数: 0

AMOTL1 -Associated Multiple Congenital Anomalies (Craniofaciocardiohepatic Syndrome, CFCHS): A Novel Clinical Spectrum Including Craniofacial, Heart and Liver Abnormalities. AMOTL1相关多发性先天畸形（颅面心肝综合征，CFCHS）：包括颅面、心脏和肝脏异常的新临床谱系。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-01 Epub Date: 2024-11-13 DOI: 10.1111/cge.14644

Natalia Gallego-Zazo, Jair Tenorio-Castano, Alejandro Parra, Julián Nevado, Mario Cazalla, Elsa Lucas-Castro, Karen E Heath, María Palomares, Emma Soengas, M Dolores Lledín, Emily Larrea, Antonio Olveira, Beatriz Morte, Ángel Carracedo, Pablo Lapunzina

引用次数: 0

PathVar: A Customisable NGS Variant Calling Algorithm Implicates Novel Candidate Genes and Pathways in Hemiplegic Migraine. PathVar：可定制的 NGS 变异调用算法揭示了偏瘫性偏头痛的新型候选基因和通路。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-01 Epub Date: 2024-10-12 DOI: 10.1111/cge.14625

Mohammed M Alfayyadh, Neven Maksemous, Heidi G Sutherland, Rodney A Lea, Lyn R Griffiths

{"title":"PathVar: A Customisable NGS Variant Calling Algorithm Implicates Novel Candidate Genes and Pathways in Hemiplegic Migraine.","authors":"Mohammed M Alfayyadh, Neven Maksemous, Heidi G Sutherland, Rodney A Lea, Lyn R Griffiths","doi":"10.1111/cge.14625","DOIUrl":"10.1111/cge.14625","url":null,"abstract":"The exponential growth of next-generation sequencing (NGS) data requires innovative bioinformatics approaches to unravel the genetic underpinnings of diseases. Hemiplegic migraine (HM), a debilitating neurological disorder with a genetic basis, is one such condition that warrants further investigation. Notably, the genetic heterogeneity of HM is underscored by the fact that approximately two-thirds of patients lack pathogenic variants in the known causal ion channel genes. In this context, we have developed PathVar, a novel bioinformatics algorithm that harnesses publicly available tools and software for pathogenic variant discovery in NGS data. PathVar integrates a suite of tools, including HaplotypeCaller from the Genome Analysis Toolkit (GATK) for variant calling, Variant Effect Predictor (VEP) and ANNOVAR for variant annotation, and TAPES for assigning the American College of Medical Genetics and Genomics (ACMG) pathogenicity labels. Applying PathVar to whole exome sequencing data from 184 HM patients, we detected 648 variants that are probably pathogenic in multiple patients. Moreover, we have identified several candidate genes for HM, many of which cluster around the Rho GTPases pathway. Future research can leverage PathVar to generate high quality, candidate pathogenic variants, which may enhance our understanding of HM and other complex diseases.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":"157-168"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459583","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

Chromosome 8p Syndromes Clinical Presentation and Management Guidelines. 染色体 8p 综合征临床表现和处理指南。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-01 Epub Date: 2024-10-10 DOI: 10.1111/cge.14626

Kourtney Santucci, Kristina E Malik, Katie Angione, Dana Bennink, Andrea Gerk, Drew Mancini, Megan Stringfellow, Tristen Dinkel, Scott Demarest, Andrea S Miele, Margarita Saenz

引用次数: 0