Global Medical Genetics最新文献

{"title":"Expert Consensus on the Diagnosis and Treatment of <i>NRG1/2</i> Gene Fusion Solid Tumors.","authors":"Chunwei Xu, Qian Wang, Dong Wang, Wenxian Wang, Wenfeng Fang, Ziming Li, Aijun Liu, Jinpu Yu, Wenzhao Zhong, Zhijie Wang, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Xiuyu Cai, Anwen Liu, Wen Li, Ping Zhan, Hongbing Liu, Tangfeng Lv, Liyun Miao, Lingfeng Min, Yu Chen, Jingping Yuan, Feng Wang, Zhansheng Jiang, Gen Lin, Long Huang, Xingxiang Pu, Rongbo Lin, Weifeng Liu, Chuangzhou Rao, Dongqing Lv, Zongyang Yu, Xiaoyan Li, Chuanhao Tang, Chengzhi Zhou, Junping Zhang, Junli Xue, Hui Guo, Qian Chu, Rui Meng, Jingxun Wu, Rui Zhang, Jin Zhou, Zhengfei Zhu, Yongheng Li, Hong Qiu, Fan Xia, Yuanyuan Lu, Xiaofeng Chen, Rui Ge, Enyong Dai, Yu Han, Weiwei Pan, Fei Pang, Qingqing He, Jintao Huang, Kai Wang, Fan Wu, Bingwei Xu, Liping Wang, Youcai Zhu, Li Lin, Yanru Xie, Xinqing Lin, Jing Cai, Ling Xu, Jisheng Li, Xiaodong Jiao, Kainan Li, Jia Wei, Huijing Feng, Lin Wang, Yingying Du, Wang Yao, Xuefei Shi, Xiaomin Niu, Dongmei Yuan, Yanwen Yao, Jianhui Huang, Yue Feng, Yinbin Zhang, Pingli Sun, Hong Wang, Mingxiang Ye, Zhaofeng Wang, Yue Hao, Zhen Wang, Bin Wan, Donglai Lv, Shengjie Yang, Jin Kang, Jiatao Zhang, Chao Zhang, Juanjuan Ou, Lin Shi, Yina Wang, Bihui Li, Zhang Zhang, Zhongwu Li, Zhefeng Liu, Nong Yang, Lin Wu, Huijuan Wang, Gu Jin, Guansong Wang, Jiandong Wang, Meiyu Fang, Yong Fang, Yuan Li, Xiaojia Wang, Yiping Zhang, Xixu Zhu, Yi Shen, Shenglin Ma, Biyun Wang, Lu Si, Yong Song, Yuanzhi Lu, Jing Chen, Zhengbo Song","doi":"10.1055/s-0044-1781457","DOIUrl":"10.1055/s-0044-1781457","url":null,"abstract":"<p><p>The fusion genes <i>NRG1</i> and <i>NRG2</i> , members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, <i>NRG1</i> retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of <i>NRG1</i> gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting <i>NRG1</i> and <i>NRG2</i> gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying <i>NRG1</i> -positive patients. Currently, there are no approved targeted drugs for <i>NRG1</i> and <i>NRG2</i> . Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of <i>NRG1</i> and <i>NRG2</i> in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with <i>NRG1</i> and <i>NRG2</i> gene fusion solid tumors.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10898996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Modifications of Developmental Dyslexia and Its Representation Using In Vivo, In Vitro Model.","authors":"Zakiyyah M M Zaki, Siti A Ali, Mazira M Ghazali, Faidruz A Jam","doi":"10.1055/s-0044-1781456","DOIUrl":"10.1055/s-0044-1781456","url":null,"abstract":"<p><p>Dyslexia is a genetic and heritable disorder that has yet to discover the treatment of it, especially at the molecular and drug intervention levels. This review provides an overview of the current findings on the environmental and genetic factors involved in developmental dyslexia. The latest techniques used in diagnosing the disease and macromolecular factors findings may contribute to a higher degree of development in detangling the proper management and treatment for dyslexic individuals. Furthermore, this review tried to put together all the models used in the current dyslexia research for references in future studies that include animal models as well as in vitro models and how the previous research has provided consistent data across many years and regions. Thus, we suggest furthering the studies using an organoid model based on the existing gene polymorphism, pathways, and neuronal function input.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10898997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Novel Risk Variants of Inflammatory Factors Related to Myeloproliferative Neoplasm: A Bidirectional Mendelian Randomization Study.","authors":"Yang Li, Ting Sun, Jia Chen, Lei Zhang","doi":"10.1055/s-0044-1779665","DOIUrl":"10.1055/s-0044-1779665","url":null,"abstract":"<p><p>Epidemiological and experimental evidence has linked chronic inflammation to the etiology of myeloproliferative neoplasm (MPN). However, it remains unclear whether genetic associations with specific inflammatory biomarkers are causal or due to bias. This study aimed to assess the effect of C-reactive protein (CRP) and systemic inflammatory regulators on MPN within a bidirectional Mendelian randomization design. Genetic associations with MPN were derived from a publicly available genome-wide association study (GWAS) comprising 1,086 cases and 407,155 controls of European ancestry. Additionally, data on inflammation were extracted from two GWASs focusing on CRP and cytokines. The causal relationships between exposure and outcome were explored using the inverse variance weighted (IVW) method. To confirm the final results, multiple sensitivity analyses, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO), were simultaneously employed. Our results suggest that lower levels of macrophage-migration inhibitory factor (IVW estimate odds ratio [OR IVW] per SD genetic cytokines change: 0.641; 95% confidence interval [CI]: 0.427-0.964; <i>p</i>  = 0.032) and higher levels of interleukin-2 receptor α (lL2Rα, 1.377, 95% CI: 1.006-1.883; <i>p</i>  = 0.046) are associated with an increased risk of MPN. Genetically predicted MPN is related to increased levels of RANTES (IVW estimate β: 0.043, 95% CI: 0.002-0.084; <i>p</i>  = 0.039) and interleukin-10 (IVW estimate β: 0.030, 95% CI: 0.001-0.060; <i>p</i>  = 0.041). This study provides evidence for a causal relationship between CRP, systemic inflammatory regulators, and MPN, and new insights into the etiology, prevention, and prognosis of MPN.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10861317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Cytogenetics Aberrations and <i>IGHV</i> Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting.","authors":"Carolina Muñoz-Novas, Isabel González-Gascón-Y-Marín, Iñigo Figueroa, Laura Sánchez-Paz, Claudia Pérez-Carretero, Miguel Quijada-Álamo, Ana-Eugenia Rodríguez-Vicente, María-Stefania Infante, María-Ángeles Foncillas, Elena Landete, Juan Churruca, Karen Marín, Victoria Ramos, Alejandro Sánchez Salto, José-Ángel Hernández-Rivas","doi":"10.1055/s-0044-1779668","DOIUrl":"10.1055/s-0044-1779668","url":null,"abstract":"<p><p>Immunoglobulin heavy chain variable ( <i>IGHV</i> ) region mutations, <i>TP53</i> mutation, fluorescence in situ hybridization (FISH), and cytogenetic analysis are the most important prognostic biomarkers used in chronic lymphocytic leukemia (CLL) patients in our daily practice. In real-life environment, there are scarce studies that analyze the correlation of these factors with outcome, mainly referred to time to first treatment (TTFT) and overall survival (OS). This study aimed to typify <i>IGHV</i> mutation status, family usage, FISH aberrations, and complex karyotype (CK) and to analyze the prognostic impact in TTFT and OS in retrospective study of 375 CLL patients from a Spanish cohort. We found unmutated CLL (U-CLL) was associated with more aggressive disease, shorter TTFT (48 vs. 133 months, <i>p</i>  < 0.0001), and shorter OS (112 vs. 246 months, <i>p</i>  < 0.0001) than the mutated CLL. <i>IGHV3</i> was the most frequently used <i>IGHV</i> family (46%), followed by <i>IGHV1</i> (30%) and <i>IGHV4</i> (16%). <i>IGHV5-51</i> and <i>IGHV1-69</i> subfamilies were associated with poor prognosis, while <i>IGHV4</i> and <i>IGHV2</i> showed the best outcomes. The prevalence of CK was 15% and was significantly associated with U-CLL. In the multivariable analysis, <i>IGHV2</i> gene usage and del13q were associated with longer TTFT, while VH1-02, +12, del11q, del17p, and U-CLL with shorter TTFT. Moreover, VH1-69 usage, del11q, del17p, and U-CLL were significantly associated with shorter OS. A comprehensive analysis of genetic prognostic factors provides a more precise information on the outcome of CLL patients. In addition to FISH cytogenetic aberrations, <i>IGHV</i> and <i>TP53</i> mutations, <i>IGHV</i> gene families, and CK information could help clinicians in the decision-making process.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10861322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Health Care Disparities in Genetic Testing and Research for Hereditary Cardiomyopathy: Current State and Future Perspectives.","authors":"Helen Huang, Jay Verma, Valerie Mok, Hareesha R Bharadwaj, Maen M Alrawashdeh, Adarsh Aratikatla, Sourav Sudan, Suprateeka Talukder, Minatoullah Habaka, Gary Tse, Mainak Bardhan","doi":"10.1055/s-0044-1779469","DOIUrl":"https://doi.org/10.1055/s-0044-1779469","url":null,"abstract":"<p><p><b>Background</b>  Hereditary cardiomyopathies are commonly occurring myocardial conditions affecting heart structure and function with a genetic or familial association, but the etiology is often unknown. Cardiomyopathies are linked to significant mortality, requiring robust risk stratification with genetic testing and early diagnosis. <b>Hypothesis</b>  We hypothesized that health care disparities exist in genetic testing for hereditary cardiomyopathies within clinical practice and research studies. <b>Methods</b>  In a narrative fashion, we conducted a literature search with online databases such as PubMed/MEDLINE, Google Scholar, EMBASE, and Science Direct on papers related to hereditary cardiomyopathies. A comprehensive analysis of findings from articles in English on disparities in diagnostics and treatment was grouped into four categories. <b>Results</b>  Racial and ethnic disparities in research study enrollment and health care delivery favor White populations and higher socioeconomic status, resulting in differences in the development and implementation of effective genetic screening. Such disparities have shown to be detrimental, as minorities often suffer from disease progression to heart failure and sudden cardiac death. Barriers related to clinical genetic testing included insurance-related issues and health illiteracy. The underrepresentation of minority populations extends to research methodologies, as testing in ethnic minorities resulted in a significantly lower detection rate and diagnostic yield, as well as a higher likelihood of misclassification of variants. <b>Conclusions</b>  Prioritizing minority-based participatory research programs and screening protocols can address systemic disparities. Diversifying research studies can improve risk stratification strategies and impact clinical practice.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10834107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139673198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Multifaceted Role of Oxytocinergic System and <i>OXTR</i> Gene.","authors":"Rakibul Hasan","doi":"10.1055/s-0044-1779039","DOIUrl":"10.1055/s-0044-1779039","url":null,"abstract":"<p><p>The article explores the multifaceted role of the neuropeptide oxytocin in human behavior and its connection to the oxytocin receptor ( <i>OXTR</i> ) gene. Oxytocin, produced in specific brain nuclei, is implicated in emotional, social, and maternal behaviors, stress reduction, uterine contraction during childbirth, and lactation. The <i>OXTR</i> gene, located on chromosome 3, encodes oxytocin receptors found in various body parts, including critical brain regions associated with social behaviors. The article delves into studies on rodents, revealing correlations between <i>OXTR</i> gene expression and pair bonding in the prefrontal cortex and social behavior regulation in the amygdala. The discussion extends to the impact of oxytocin on social support-seeking behavior, focusing on a specific genetic variation, rs53576. The article explores how this genetic variation influences empathy, stress reactivity, and susceptibility to disorders such as autism and social anxiety. Furthermore, the article examines structural and functional changes in the brain associated with <i>OXTR</i> gene variations. It discusses the role of DNA methylation in influencing oxytocin receptor availability, affecting social perception and responsiveness to negative stimuli. The article also highlights the oxytocinergic system's involvement in disorders such as autism and social anxiety, emphasizing the interplay between genetics and environmental factors. The article also touches on the potential therapeutic use of exogenous oxytocin in mitigating symptoms associated with these disorders. In summary, the article underscores the intricate relationship between oxytocin, the <i>OXTR</i> gene, and diverse aspects of human behavior, providing insights into social bonding, perception, and the development of behavioral disorders.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the Pentapeptide as the Measurement Unit in Immunology.","authors":"Darja Kanduc","doi":"10.1055/s-0044-1779041","DOIUrl":"10.1055/s-0044-1779041","url":null,"abstract":"<p><p>This communication concerns a crucial query in immunology, that is, the dimension of an epitope. The issue has essential implications in vaccine formulations.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Variants of CEP152 in a Case of Compound-Heterozygous Inheritance of Epilepsy.","authors":"Weiran Li, Xiaowei Lu, Jianbo Shu, Yingzi Cai, Dong Li, Chunquan Cai","doi":"10.1055/s-0043-1777807","DOIUrl":"10.1055/s-0043-1777807","url":null,"abstract":"<p><p><b>Introduction</b>   <i>CEP152</i> encodes protein Cep152, which associates with centrosome function. The lack of Cep152 can cause centrosome duplication to fail. <i>CEP152</i> mutates, causing several diseases such as Seckel syndrome-5 and primary microencephaly-9. <b>Methods</b>  In this study, we reported a patient diagnosed with epilepsy in Tianjin Children's Hospital. We performed clinical examination and laboratory test, and whole-exome sequencing was performed for the proband's and his parents' peripheral blood. The suspected compound-heterozygous variant in the <i>CEP152</i> gene was verified by Sanger sequencing and quantitative real-time polymerase chain reaction technology. <b>Results</b>  We discovered three variants-two of them from <i>CEP152</i> and one from <i>HPD</i> . The result showed the variants in <i>CEP152</i> only. The patient presented with seizures frequently. Sanger sequencing showed two novel variants in <i>CEP152</i> are in exon26 (NM_014985.3 c.3968C > A p.Ser1323*) and in exon16 (NM_014985.3 c.2034_2036del p.Tyr678*). <b>Conclusions</b>  We reported a novel compound-heterozygous variant in the <i>CEP152</i> gene in this study. Most of the phenotypes are Seckel syndrome and primary microencephaly, and the novel variant may cause an atypical phenotype that is epilepsy.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10791487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pair of Compound Heterozygous <i>IARS2</i> Variants Manifesting West Syndrome and Electrolyte Disorders in a Chinese Patient.","authors":"Feiyu Zhou, Gui Yi, Xiangyu Liu, Wenchao Sheng, Jianbo Shu, Dong Li, Chunquan Cai","doi":"10.1055/s-0043-1778091","DOIUrl":"10.1055/s-0043-1778091","url":null,"abstract":"<p><p><b>Background</b>  Aminoacyl-tRNA synthetases (ARSs) are evolutionarily conserved enzymes that ensure the accuracy of the translation process. Isoleucyl-tRNA synthetase 2 ( <i>IARS2</i> ) gene is a type of ARS that encodes mitochondrial isoleucine-tRNA synthetase. Pathogenic variants in the <i>IARS2</i> gene are associated with mitochondrial disease which involves several patients presenting broad clinical phenotypes. These clinical phenotypes include West syndrome, Leigh syndrome, and Cataract, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia syndrome. Only 29 cases have been reported worldwide. The patient manifested recurrent convulsions, and specific clinical manifestations included electrolyte disorders and recurrent infections. <b>Methods</b>  Whole-exome sequencing was performed on the child with West syndrome. Three-dimensional structure reconstruction and thermodynamic stability prediction were performed to further analyze the relationship between variation and phenotype. <b>Conclusion</b>  This study further expands the clinical spectrum of <i>IARS2</i> pathogenic variants. The case summaries help raise clinical awareness of <i>IARS2</i> -associated disease and reduce misdiagnosis. <b>Result</b>  In this report, a 13-month-old girl was diagnosed with West syndrome and Leigh syndrome for 7 months. Compound heterozygous variants in the IARS2 gene (NM_018060.4), c.2450G>A (Arg817His) and copy number variation (NC_000001. 11: g. (220267549_220284289) del), were detected by WES. This study further expands the clinical spectrum of IARS2 pathogenic variants. The case summaries help raise clinical awareness of IARS2-associated disease and reduce misdiagnosis.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10791488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Two Variants c.2697A > C and c.3305A > C in USP7 by Analysis of Whole-Exome Sequencing in Chinese Patients with Hao-Fountain Syndrome.","authors":"Mei Sun, Qing Li, Ying Zhang, Yingzi Cai, Yan Dong, Jianbo Shu, Dong Li, Chunquan Cai","doi":"10.1055/s-0043-1778089","DOIUrl":"10.1055/s-0043-1778089","url":null,"abstract":"<p><p><b>Background</b>  Variants of ubiquitin-specific protease 7 ( <i>USP7</i> ) gene in humans are associated with a neurodevelopmental disorder-Hao-Fountain syndrome, its core symptoms including developmental delay, intellectual disability, and speech delay. Other variable symptoms can affect multiple systems. In present study, we report two patients with core features from two unrelated consanguineous families originating from the Tianjin Children's Hospital. <b>Methods and Results</b>  Genomic DNA was extracted from the peripheral blood samples collected from the probands with their family members and whole-exome sequencing (WES) was used to detect the pathogenic genes in the probands. Suspected variants were subsequently validated by Sanger sequencing. In family 1, WES revealed that the proband carried the de novo variant c.2697A > C (p.Leu899Phe) in <i>USP7</i> (NM_003470.3). In family 2, WES identified the variant c.3305A > C (p.Asn1102Thr) in <i>USP7</i> (NM_003470.3) from the proband. <b>Conclusion</b>  We reported two cases of Hao-Fountain syndrome caused by novel <i>USP7</i> variants. In addition, we report the first case of mosaicism with a <i>USP7</i> variant in Chinese family. Our findings demonstrate the importance of WES in diagnosis of genetic diseases and expands the <i>USP7</i> variants spectrum in Hao-Fountain syndrome. Moreover, we summarize the cases caused by <i>USP7</i> variants in the literature. Our study can provide a vital reference for the diagnosis of future cases.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10791489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}