Clinical Genetics最新文献_第5页

Evaluating the Clinical Utility of Genomic Sequencing After Perinatal Death. 围产儿死亡后基因组测序的临床应用评估。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-08-09 DOI: 10.1111/cge.70028

Camille M Schubert, Matilda R Jackson, Christopher P Barnett, Hamish S Scott, Thomas Sullivan, Stephen Goodall, Tracy Merlin

{"title":"Evaluating the Clinical Utility of Genomic Sequencing After Perinatal Death.","authors":"Camille M Schubert, Matilda R Jackson, Christopher P Barnett, Hamish S Scott, Thomas Sullivan, Stephen Goodall, Tracy Merlin","doi":"10.1111/cge.70028","DOIUrl":"https://doi.org/10.1111/cge.70028","url":null,"abstract":"Following termination of pregnancy for fetal anomaly or unexplained perinatal death (PND), clinical geneticists advise on possible genetic causes and likelihood of recurrence, often with limited use of molecular analysis. In the Australian Genomic Autopsy Study (GAS) cases that were unresolved following standard-of-care investigations underwent exome and/or genome sequencing (ES/GS). This diagnostic before-and-after study measured the changes in clinical management, in terms of the effect on clinical counselling that was provided to parents following ES/GS. Clinicians were surveyed before and after receiving sequencing results about the likelihood of recurrence and the reproductive planning advice they would provide to families. 161 pairs of before-and-after surveys were completed. Clinician estimates regarding PND recurrence changed for 45% (73/161) of families after receiving test results, despite a genetic diagnosis being found in only 19%. Families with an 'unknown likelihood' of recurrence reduced from 26% to 15% (p = 0.01). The information provided to parents about recurrence and reproductive planning increased significantly, both with and without a diagnosis, and clinicians reported that most parents expressed value was obtained from the investigation. The utility of genomic autopsy for clinical management is not restricted to families with a genetic finding.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803748","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

Pathogenic Variants in Mennonites From Southern Brazil: Implications for Preventive Measures in Public Health. 巴西南部门诺派教徒的致病变异：对公共卫生预防措施的影响。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-08-05 DOI: 10.1111/cge.70035

Luiza Beatriz Mayer de Lima, Eduardo Delabio Auer, Isabela Dall'Oglio Bucco, Valéria Bumiller-Bini Hoch, Priscila Ianzen Dos Santos, Fabiana L Lopes, Alan Shuldiner, Emilton Lima Júnior, Angelica Beate Winter Boldt

{"title":"Pathogenic Variants in Mennonites From Southern Brazil: Implications for Preventive Measures in Public Health.","authors":"Luiza Beatriz Mayer de Lima, Eduardo Delabio Auer, Isabela Dall'Oglio Bucco, Valéria Bumiller-Bini Hoch, Priscila Ianzen Dos Santos, Fabiana L Lopes, Alan Shuldiner, Emilton Lima Júnior, Angelica Beate Winter Boldt","doi":"10.1111/cge.70035","DOIUrl":"https://doi.org/10.1111/cge.70035","url":null,"abstract":"The Mennonite population has a unique history of 500 years of genetic isolation shaped by at least three demographic bottlenecks, founder effects, inbreeding, epidemics, and migrations. To evaluate their susceptibility for monogenic diseases (MD), we performed whole-exome sequencing on 325 volunteers from two South Brazilian Mennonite settlements (one urban and another rural). We identified 23 pathogenic variants (P) and 27 likely P, with 22.8% accounting for endocrine, nutritional, and metabolic MDs, 17.5% for developmental anomalies, and 10.5% for nervous system MDs. HFE rs1800562 causing hereditary hemochromatosis presented the highest frequency (7.54%), followed by BTD rs13078881 for biotinidase deficiency (7.08%), FLG rs61816761 for ichthyosis vulgaris and atopic dermatitis (3.38%), and FANCM rs147021911 for Fanconi anemia (3.08%). Genomic and genealogical analysis confirmed their European origin, with very low consanguinity and high heterozygosity coefficients, confirming a random selection of refugees that emigrated from widespread settlements in Russia to Brazil in 1930. There was also a slight deviation to Native Americans for self-reported admixed Mennonites. Even so, founder effects occurred for 96% of P, whose frequencies differed from non-Finnish Europeans, Amish, and Brazilian populations. These findings highlight the genetic risks in this population, reinforcing the importance of genetic counseling, screening programs, and Personalized and Preventive Medicine strategies to mitigate health risks associated with inherited conditions.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788413","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

Avascular Necrosis and Minimal Trauma Fractures in Telomere Biology Disorders. 端粒生物学疾病中的缺血性坏死和轻微创伤骨折。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-08-05 DOI: 10.1111/cge.70038

Arman M Niknafs, Neelam Giri, Marena R Niewisch, Sharon A Savage

{"title":"Avascular Necrosis and Minimal Trauma Fractures in Telomere Biology Disorders.","authors":"Arman M Niknafs, Neelam Giri, Marena R Niewisch, Sharon A Savage","doi":"10.1111/cge.70038","DOIUrl":"https://doi.org/10.1111/cge.70038","url":null,"abstract":"Avascular necrosis (AVN) and minimal trauma fractures (MTF) cause significant morbidity in patients with telomere biology disorders (TBDs). TBDs are associated with very high risks of bone marrow failure, pulmonary fibrosis, cancer, and many other complications due to pathogenic germline variants in genes essential for telomere function and maintenance. To understand the extent to which AVN and MTF occur in TBDs and identify areas requiring more research in the role of telomeres in bone biology. We assessed the occurrence of AVN and MTF in 233 patients with TBDs. An age, gender, and gene-matched TBD patient control group was used to assess associations between AVN/MTF and clinical characteristics. Forty-two (18%) patients with TBD developed at least one AVN and/or MTF event with 19 patients experiencing their first event in childhood. AVN and MTF were most common in patients with autosomal or X-linked recessive, or heterozygous TINF2 disease (19/36 AVN and 17/19 MTF). Androgen and corticosteroid use were more common in patients with AVN compared with matched patient controls (41.2% vs. 16.3%, p < 0.05 and 41.2% vs. 14%, p < 0.01, respectively); however, 57.1% of patients experienced AVN and/or MTF events in the absence of androgen or corticosteroid use. Severe bone marrow failure and hematopoietic cell transplantation history were significantly more common in MTF patients than in controls (44.2% and 30.2% respectively, p < 0.05). There were no statistically significant associations between low bone mineral density or vitamin D deficiency and AVN or MTF. AVN and MTFs are common, debilitating complications in TBDs and frequently occur independently of androgen or corticosteroid use. Our results underscore the need for disease-specific translational studies as well as improved prevention and therapeutic options for patients with TBDs. Trial Registration: ClinicalTrials.gov identifier: NCT00027274.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783641","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

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-08-05 DOI: 10.1111/cge.70039

Rahi Patel, Rikhil Makwana, Elaine Marchi, Ziyi Fan, Erin Falsey, Beatriz Menendez, Philip Giampietro, Ingrid M Wentzensen, Tzung-Chien Hsieh, Shu-Ou Shan, Gholson J Lyon

引用次数: 0

Genetic Characterization of Lithuanian Patients With Cystic Kidney. 立陶宛囊肾患者的遗传特征。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-08-04 DOI: 10.1111/cge.70036

Deimante Brazdziunaite, Gabija Mazur, Agne Kerpauskiene, Rimante Cerkauskiene, Loreta Vareikiene, Marius Miglinas, Algirdas Utkus

{"title":"Genetic Characterization of Lithuanian Patients With Cystic Kidney.","authors":"Deimante Brazdziunaite, Gabija Mazur, Agne Kerpauskiene, Rimante Cerkauskiene, Loreta Vareikiene, Marius Miglinas, Algirdas Utkus","doi":"10.1111/cge.70036","DOIUrl":"https://doi.org/10.1111/cge.70036","url":null,"abstract":"Cystic kidney diseases are genetically and clinically heterogeneous. Despite advances in genetic testing, some patients remain undiagnosed, limiting targeted care. This study explores the genetic causes in Lithuanian patients with multiple kidney cysts. Genetic testing using kidney-focused next-generation sequencing or Sanger sequencing was performed on 114 patients. Genetic and clinical data from individuals with detected variants were analyzed. Diagnostic variants were identified in 69% of families; variants of uncertain significance in 13%, and the remaining families were undiagnosed. The diagnostic yield was 73% in Group 1 (defined cystic kidney phenotype) and 61% in Group 2 (nonspecific kidney cysts). In total, 24 novel variants were identified in seven genes. Autosomal dominant polycystic kidney disease (ADPKD) was the most common diagnosis. Among patients with nonspecific cysts, variants were found in PKD1, COL4A5, HNF1B, NPHP1, PAX2, TSC2, and UMOD, while 39% remained genetically unresolved. Patients with non-ADPKD diagnoses typically showed multiple cysts without a definitive phenotype. Most patients harbored disease-causing variants, with novel variants that will contribute to the ADPKD Variant Database. While ciliopathies are frequently recognized, genetic glomerulopathies may also present with a cystic phenotype. Genetic testing should be considered in cases of nonspecific multiple kidney cysts.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783642","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

Loss of Different Domains of TDRD12 Leads to Distinct Male Infertility-Related Phenotypes. TDRD12不同结构域的缺失导致不同的男性不育相关表型。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-08-01 DOI: 10.1111/cge.70034

Xinyao Tang, Jinhui Li, Yunchuan Tian, Chanjuan Zhao, Xiaohui Jiang, Chuan Jiang, Xiang Wang, Jun Ma, Yingteng Zhang, Tiechao Ruan, Guicheng Zhao, Yihong Yang, Ying Shen

{"title":"Loss of Different Domains of TDRD12 Leads to Distinct Male Infertility-Related Phenotypes.","authors":"Xinyao Tang, Jinhui Li, Yunchuan Tian, Chanjuan Zhao, Xiaohui Jiang, Chuan Jiang, Xiang Wang, Jun Ma, Yingteng Zhang, Tiechao Ruan, Guicheng Zhao, Yihong Yang, Ying Shen","doi":"10.1111/cge.70034","DOIUrl":"https://doi.org/10.1111/cge.70034","url":null,"abstract":"Tdrd12 is known to play an important role in spermatogenesis in mice. However, evidence linking TDRD12 mutations to male azoospermia is limited, and no cases of TDRD12-related teratozoospermia have been reported. We identified two novel homozygous TDRD12 mutations (c.3378dupG and c.2463C>G) in two unrelated infertile men, respectively. Patient 1 carried a TDRD12 frameshift mutation (c.3378dupG), resulting in a truncated protein lacking the cysteine-rich domain. This patient presented with teratozoospermia, characterized by abnormal sperm morphology, including defects in the head and flagellum. Patient 2 carried a TDRD12 nonsense mutation (c.2463C>G), resulting in complete degradation of the protein. This patient exhibited azoospermia, characterized by germ cell maturation arrest at the spermatocyte stage. Mechanistically, TDRKH, TDRD9, PIWIL2, and PIWIL1, key piRNA biogenesis proteins, are predicted to interact with TDRD12. Notably, PIWIL1 fluorescence was reduced in Patient 1's sperm, while PIWIL2 and TDRD9 signals were diminished and LINE-1 signal was increased in Patient 2's testicular tissue. Furthermore, Intracytoplasmic sperm injection using Patient 1's sperm was unsuccessful. Our study first identified that the loss of different domains of TDRD12 results in distinct male infertility-related phenotypes. These findings revealed novel genetic insights into male infertility, demonstrated the critical role of TDRD12 in human spermatogenesis, and are helpful for diagnosis and genetic counseling.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764684","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

Comprehensive Clinical Characteristics, Longitudinal Adaptive Functioning, and Electroencephalogram Activity in MAPK8IP3-Related Neurodevelopmental Disorder. mapk8ip3相关神经发育障碍的综合临床特征、纵向适应功能和脑电图活动

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-07-29 DOI: 10.1111/cge.70032

Khemika K Sudnawa, Alexa Geltzeiler, Cara H Kanner, Kyle Zreibe, Nicolò Pini, Celia Tam, Robert J Fee, Sean Calamia, Emily Callejo, Holli Sharples, Catherine E Serianni, Michela Fagiolini, Ellen Hanson, Jacqueline Montes, April Levin, Wendy K Chung

{"title":"Comprehensive Clinical Characteristics, Longitudinal Adaptive Functioning, and Electroencephalogram Activity in MAPK8IP3-Related Neurodevelopmental Disorder.","authors":"Khemika K Sudnawa, Alexa Geltzeiler, Cara H Kanner, Kyle Zreibe, Nicolò Pini, Celia Tam, Robert J Fee, Sean Calamia, Emily Callejo, Holli Sharples, Catherine E Serianni, Michela Fagiolini, Ellen Hanson, Jacqueline Montes, April Levin, Wendy K Chung","doi":"10.1111/cge.70032","DOIUrl":"https://doi.org/10.1111/cge.70032","url":null,"abstract":"Mitogen-activated protein kinase 8-interacting protein 3-related neurodevelopmental disorder (MAPK8IP3-related NDD) results from heterozygous pathogenic or likely pathogenic variants in MAPK8IP3. We report on 32 individuals (median age 7.5 years, range 1.3-22.0), all of whom had heterozygous pathogenic/likely pathogenic MAPK8IP3 variants, including missense (62.5%) and predicted loss-of-function (LOF) variants (34.4%). Common symptoms included cognitive impairment, hypotonia, motor difficulties, strabismus, microcephaly, and attention deficits. Corpus callosum thinning was reported in 62.1%. Nearly all individuals walked independently but demonstrated slower gait speed and a wider base of support compared to controls. The mean DAS-II General Conceptual Ability score was 62.5 ± 26.5. EEG analysis suggested a trend toward lower power accentuated frequency compared to typically developing individuals. Missense variants were associated with more severe symptoms than LOF variants. This study provides valuable insights into the clinical characteristics, patient management, and preparation for future clinical trials.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741353","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

Pathogenic DDX39A Variant Disrupts Nuclear Homeostasis and Causes an Early-Onset Neurodegenerative Disorder With Cerebral Atrophy. 致病性DDX39A变异破坏核稳态并导致早发性神经退行性疾病伴脑萎缩

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-07-29 DOI: 10.1111/cge.70033

S Rehan Ahmad, Abdullah M AlShahrani, Natchimuthu Vijayakumar, Anupriya Kumari

{"title":"Pathogenic DDX39A Variant Disrupts Nuclear Homeostasis and Causes an Early-Onset Neurodegenerative Disorder With Cerebral Atrophy.","authors":"S Rehan Ahmad, Abdullah M AlShahrani, Natchimuthu Vijayakumar, Anupriya Kumari","doi":"10.1111/cge.70033","DOIUrl":"https://doi.org/10.1111/cge.70033","url":null,"abstract":"Neurodevelopmental disorders arising from mutations in RNA-processing factors are increasingly recognized but remain mechanistically underexplored. Here, we identify that variant (c.485A>C; p.Lys137Gln) in DDX39A in a 7-month-old proband presenting with global developmental delay, microcephaly, seizures, hypotonia, and brain atrophy with corpus callosum thinning. DDX39A encodes a DEAD-box RNA helicase essential for mRNA splicing and export via the TREX complex. Functional studies in proband-derived fibroblasts revealed that while transcript and protein levels of DDX39A-K137Q were unaffected, the mutant protein displayed aberrant nuclear clumping and failed to interact with the TREX component THOC1. Structural modeling demonstrated that Lys137 mediates critical inter- and intra-molecular interactions, which are disrupted by the K137Q substitution. This loss destabilizes the DDX39A-THOC1 interface, impairing TREX complex integrity. The mutant cells exhibited severe nuclear morphological abnormalities, disrupted nuclear lamina organization, and increased cell death. Transcriptomic network analysis and gene ontology revealed enrichment of DDX39A interactions in mRNA export, splicing, and nucleocytoplasmic transport-functions essential for neuronal development. Temporal and regional brain expression data showed that DDX39A is highly expressed during early postnatal life and across multiple brain regions, indicating its importance in early brain maturation. Our findings establish DDX39A-K137Q as a pathogenic variant that impairs nuclear RNA processing and structural homeostasis, leading to a severe neurodegenerative phenotype. This study identifies the role of RNA helicases in neurodevelopment and explores DDX39A as a novel gene implicated in pediatric neurodegenerative disease.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728417","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

Hypohidrotic Ectodermal Dysplasias: Phenotypic and Genotypic Findings in 32 Cases. 32例少汗性外胚层发育不良的表型和基因型分析。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-07-23 DOI: 10.1111/cge.70030

Zeynep Esener, Mehmet Akif Yücesoy, Alper Gezdirici, Mustafa Dogan, Ayberk Turkyilmaz, Ibrahim Tekedereli, Hasan Bas, Aysel Tekmenuray-Unal, Sinem Kocagil, Senol Citli, Murat Ozturk, Emine Ipek Ceylan, Volkan Karaman, Ayca Dilruba Aslanger

{"title":"Hypohidrotic Ectodermal Dysplasias: Phenotypic and Genotypic Findings in 32 Cases.","authors":"Zeynep Esener, Mehmet Akif Yücesoy, Alper Gezdirici, Mustafa Dogan, Ayberk Turkyilmaz, Ibrahim Tekedereli, Hasan Bas, Aysel Tekmenuray-Unal, Sinem Kocagil, Senol Citli, Murat Ozturk, Emine Ipek Ceylan, Volkan Karaman, Ayca Dilruba Aslanger","doi":"10.1111/cge.70030","DOIUrl":"https://doi.org/10.1111/cge.70030","url":null,"abstract":"Hypohidrotic ectodermal dysplasias are a genetic condition affecting ectoderm-derived structures such as hair, teeth, nails, and sweat glands, resulting from variations in the EDA, EDAR, EDARADD, and WNT10A genes. This study examined 32 cases from 25 unrelated families from Türkiye, identifying seven novel variants in the EDA, EDAR, and WNT10A genes. The distribution of genetic alterations across the cohort revealed that 44% of the families (11/25) harbored variants in EDA, whereas EDAR and WNT10A variants were identified in 32% (8/25) and 24% (6/25) of families, respectively. Clinical evaluation revealed the characteristic hypohidrotic ectodermal dysplasia triad of hypotrichosis, hypodontia, and hypohidrosis was observed in 87.5% of cases, along with other symptoms such as dry skin, atopic dermatitis, and developmental delays. All cases presented with hair, eyebrow, and eyelash abnormalities, ranging in severity from subtle thinning to marked hypotrichosis. Among the cohort, one case exhibited severe atopic dermatitis as the predominant symptom. Targeted next-generation sequencing and clinical exome sequencing were employed to determine the genetic basis of the condition, emphasizing the importance of early diagnosis for targeted interventions. This study expands the genetic and phenotypic spectrum of hypohidrotic ectodermal dysplasia, presenting a comprehensive overview of molecular findings and genotype-phenotype correlations in the population from the Turkish population.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697800","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

French Guidelines of the AchroPuce Network for the Interpretation and Reporting of Constitutional Copy Number Variants. 宪法副本号码变体解释和报告的法文翻译网络指南。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-07-22 DOI: 10.1111/cge.70027

Céline Pebrel-Richard, Paul Kuentz, Anne-Claude Tabet, Jean-Michel Dupont, Chantal Missirian, Serge Romana, Detlef Trost, Caroline Rooryck, Valérie Malan, Matthieu Egloff

{"title":"French Guidelines of the AchroPuce Network for the Interpretation and Reporting of Constitutional Copy Number Variants.","authors":"Céline Pebrel-Richard, Paul Kuentz, Anne-Claude Tabet, Jean-Michel Dupont, Chantal Missirian, Serge Romana, Detlef Trost, Caroline Rooryck, Valérie Malan, Matthieu Egloff","doi":"10.1111/cge.70027","DOIUrl":"https://doi.org/10.1111/cge.70027","url":null,"abstract":"Over the past 15 years, molecular methods for human genome analysis have evolved significantly, becoming integral to routine genetic diagnostics. Among various genomic alterations, copy-number variations (CNVs) are particularly important as sources of both benign and pathogenic variants. Accurate assessment of these variants' clinical implications is critical, especially for rare, non-recurrent CNVs and for susceptibility loci linked to neurodevelopmental disorders (NDDs). To address these challenges, the French AchroPuce CNV Interpretation Working Group proposes a novel classification termed \"PIEV,\" referring to CNVs associated with NDDs characterized by incomplete penetrance and variable expressivity. This category complements the existing five-tier ACMG classification system, supporting genetic professionals in harmonizing practice through standardized French national guidelines, thereby enhancing genetic counseling and clinical interpretation precision. Distinguishing clearly pathogenic variants from those with incomplete penetrance is crucial, and the consistent classification of these CNVs independently of the clinical context is essential. Clinical significance assessments should entail collaboration between biologists and multidisciplinary clinical teams, especially in prenatal diagnostics. The working group maintains an annually reviewed curated list of recurrent neurodevelopmental CNVs with reduced penetrance and provides consensus recommendations with a customized interpretation tool to enhance national consistency in CNVs reporting.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682149","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