Global Medical Genetics最新文献

{"title":"46 XX Ovotesticular Disorder of Sex Development with Gonadotropin-Releasing Hormone Receptor, Autosomal Recessive Heterozygous Missense Mutation and Autosomal Dominant Heterozygous Missense Mutation of the <i>PROKR2</i> Gene: A Case Report.","authors":"Francesca Peranzoni, Roberto De Castro, Emilio Merlini, Yen Le Nguyen","doi":"10.1055/s-0044-1788060","DOIUrl":"10.1055/s-0044-1788060","url":null,"abstract":"<p><p>True hermaphroditism is a disorder of sex development (DSD), accounting for less than 5% of all DSD cases, defined by the simultaneous presence of testicular tissue and ovarian tissue in the same individual. In the reported case, the patient presented two genetic mutations involved in the pathogenic pathway of the DSD condition associated with the clinical features of Kallmann syndrome (KS), a developmental disease that associates hypogonadotropic hypogonadism (HH), due to gonadotropin-releasing hormone deficiency, and anosmia, related to the absence or hypoplasia of the olfactory bulbs. Given the variable degree of hyposmia in KS, the distinction between KS and normosmic idiopathic HH is currently unclear, especially as HH patients do not always undergo detailed olfactory testing. This syndrome is very rare, with an estimated prevalence of 1:80,000 in males and 1:40,000 in females. This is the only case report concerning a patient with 46 XX true hermaphroditism affected by HH and digenic inheritance of Kallmann syndrome.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 3","pages":"220-224"},"PeriodicalIF":1.5,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581079","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":"Recurrent Cerebral Venous Sinus Thrombosis Occurred in an Acute Lymphoblastic Leukemia Child with Mutated Lipoprotein Lipase Gene during Asparaginase Therapy.","authors":"Shiyuan Wang, Jun Li, Ying Li, Xiaoming Liu, Lixian Chang, Beibei Zhao, Li Zhang, Yao Zou, Min Ruan, Xiaofan Zhu","doi":"10.1055/s-0044-1788043","DOIUrl":"10.1055/s-0044-1788043","url":null,"abstract":"<p><p>Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 3","pages":"214-219"},"PeriodicalIF":1.5,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555651","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 Alarming Situation of Highly Pathogenic Avian Influenza Viruses in 2019-2023.","authors":"Zhiwei Zhang, Zhao Lei","doi":"10.1055/s-0044-1788039","DOIUrl":"10.1055/s-0044-1788039","url":null,"abstract":"<p><p>Avian influenza viruses (AIVs) have the potential to cause severe illness in wild birds, domestic poultry, and humans. The ongoing circulation of highly pathogenic avian influenza viruses (HPAIVs) has presented significant challenges to global poultry industry and public health in recent years. This study aimed to elucidate the circulation of HPAIVs during 2019 to 2023. Specifically, we assess the alarming global spread and continuous evolution of HPAIVs. Moreover, we discuss their transmission and prevention strategies to provide valuable references for future prevention and control measures against AIVs.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 3","pages":"200-213"},"PeriodicalIF":2.1,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471428","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":"Mesenchymal Stem Cells in Clinical Trials for Immune Disorders.","authors":"Zongjin Li, Zhibo Han, Zhong-Chao Han","doi":"10.1055/s-0044-1788044","DOIUrl":"10.1055/s-0044-1788044","url":null,"abstract":"","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 3","pages":"196-199"},"PeriodicalIF":1.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471427","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":"Comparing Genomic Profiles of <i>ALK</i> Fusion-Positive and <i>ALK</i> Fusion-Negative Nonsmall Cell Lung Cancer Patients.","authors":"Wenchao Xia, Jing Yang, Hongbin Li, Ling Li, Jinfeng Liu","doi":"10.1055/s-0044-1787301","DOIUrl":"10.1055/s-0044-1787301","url":null,"abstract":"<p><p><b>Background</b>  Anaplastic lymphoma kinase ( <i>ALK</i> ) fusion events account for 3 to 7% of genetic alterations in patients with nonsmall cell lung cancer (NSCLC). This study aimed to explore the landscape of <i>ALK</i> fusion-positive and <i>ALK</i> fusion-negative in a large cohort of NSCLC patients. <b>Methods</b>  The formalin-fixed paraffin-embedded specimens of NSCLC patients who underwent next-generation sequencing from 2020 to 2023 in Yinfeng Gene Technology Co., Ltd. Clinical laboratory were included in this study. <b>Results</b>  In the current study, a total of 180 (3.20%) patients tested positive for <i>ALK</i> fusions in 5,622 NSCLC samples. Within the <i>ALK</i> -positive cohort, a total of 228 <i>ALK</i> fusions were identified. Furthermore, five novel <i>ALK</i> fusion partners, including <i>DAB1-ALK</i> , <i>KCMF1-ALK</i> , <i>KIF13A-ALK</i> , <i>LOC643770-ALK</i> , and <i>XDH-ALK</i> were identified. In cases with <i>ALK</i> fusion-positive, <i>TP53</i> alterations were the most prevalent (26.3%), followed by <i>CDKN2A</i> (8.4%), epidermal growth factor receptor ( <i>EGFR</i> , 5.6%), and <i>ALK</i> (5.6%). By contrast, <i>EGFR</i> alterations were most prevalent (51%) in patients with <i>ALK</i> fusion-negative NSCLC, followed by <i>TP53</i> (42.7%), <i>KRAS</i> (11.6%), and <i>CDKN2A</i> (11.3%). A total of 10 cases where <i>ALK</i> fusion co-occurred with <i>EGFR</i> mutations were also identified. Notably, the <i>ALK</i> fusion positivity rate was higher in younger patients ( <i>p</i>  < 0.0001) and in female patients ( <i>p</i>  = 0.0429). Additionally, positive <i>ALK</i> test results were more prevalent in patients with high programmed death-ligand 1 expression, especially when applying a 50% cutoff. <b>Conclusions</b>  Collectively, these findings offer valuable genomic insights that could inform the personalized clinical care of patients with NSCLC harboring <i>ALK</i> fusions within the context of precision medicine.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 2","pages":"175-186"},"PeriodicalIF":1.5,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11175831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318545","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":"Clinical and Molecular Characteristics of Megakaryocytes in Myelodysplastic Syndrome.","authors":"Fangxiu Luo, Jialu Zhao, Yubao Chen, Zhenping Peng, Ran An, Yeling Lu, Jiaming Li","doi":"10.1055/s-0044-1787752","DOIUrl":"10.1055/s-0044-1787752","url":null,"abstract":"<p><p><b>Objective</b>  Myelodysplastic syndrome (MDS) is a malignant clonal disorder of hematopoietic stem cells which is characterized by morphologic dysplasia. However, the pathological characteristics of megakaryocytes (MKs) in MDS patients with gene mutation are not well established. <b>Methods</b>  Bone marrow MK specimens from 104 patients with primary MDS were evaluated, and all patients were distributed into two groups according to gene mutation associated with functional MKs. The morphologic and cellular characteristics of MKs and platelets were recorded and compared. <b>Results</b>  The more frequently mutated genes in MDS patients were <i>TUBB1</i> (11.54%), <i>VWF</i> (8.65%), <i>NBEAL2</i> (5.77%), and the most common point mutation was <i>TUBB1</i> p.(R307H) and p.(Q43P). Patients with MK mutation showed a decrease in adenosine diphosphate-induced platelet aggregation, high proportion of CD34 ⁺ CD61 ⁺ MKs (10.00 vs. 4.00%, <i>p</i>  = 0.012), and short overall survival (33.15 vs. 40.50 months, <i>p</i>  = 0.013). Further, patients with a higher percent of CD34 ⁺ CD61 ⁺ MKs (≧20.00%) had lower platelet counts (36.00 × 10 ⁹ /L vs. 88.50 × 10 ⁹ /L, <i>p</i>  = 0.015) and more profound emperipolesis ( <i>p</i>  = 0.001). By analyzing RNA-sequencing of MKs, differentially expressed mRNA was involved in physiological processes including platelet function and platelet activation, especially for MDS patients with high percent of CD34 ⁺ CD61 ⁺ MKs. The high levels of expression of CD62P, CXCL10, and S100A9 mRNA, shown by RNA sequencing, were validated by PCR assay. <b>Conclusion</b>  High proportion of CD34 ⁺ CD61 ⁺ MKs was a poor prognostic factor in MDS patients with MK mutation. CD62P, CXCL10, and S100A9 may be the potential targets to evaluate the molecular link between gene defects and platelet function.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 2","pages":"187-195"},"PeriodicalIF":1.5,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301807","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 a Novel Intronic Mutation in <i>VMA21</i> Associated with a Classical Form of X-Linked Myopathy with Autophagy.","authors":"Mainak Bardhan, Kiran Polavarapu, Dipti Baskar, Veeramani Preethish-Kumar, Seena Vengalil, Saraswati Nashi, Valakunja H Ganaraja, Dinesh Sharma, Karthik Kulanthaivelu, B N Nandeesh, Atchayaram Nalini","doi":"10.1055/s-0044-1786815","DOIUrl":"10.1055/s-0044-1786815","url":null,"abstract":"<p><p><b>Introduction</b>   <i>VMA21</i> -related myopathy is one of the rare forms of slowly progressive myopathy observed in males. Till now, there have been only a handful of reports, mainly from Europe and America, and two reports from India. <b>Method</b>  Here, we describe a case of genetically confirmed <i>VMA21</i> -associated myopathy with clinical, histopathological, and imaging features with a list of known VMA21 mutations. <b>Results</b>  A 29-year-old man had the onset of symptoms at 18 years of age with features of proximal lower limb weakness. Muscle magnetic resonance imaging showed the preferential involvement of vasti and adductor magnus. A biopsy of the left quadriceps femoris showed features of autophagic vacuolar myopathy with vacuoles containing granular eosinophilic materials. In targeted next-generation sequencing, hemizygous mutation in the 3' splice site of intron 2 of the <i>VMA21</i> gene (c.164-7 T > A) was identified and confirmed the diagnosis of X-linked myopathy with excessive autophagy. <b>Conclusion</b>  This report expands the phenotypic and genotypic profile of <i>VMA21</i> -related myopathy, with a yet unreported mutation in India.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 2","pages":"167-174"},"PeriodicalIF":1.5,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910875","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":"CRISPR-Cas9 Gene Editing: Curing Genetic Diseases by Inherited Epigenetic Modifications.","authors":"Nikhil Deep Kolanu","doi":"10.1055/s-0044-1785234","DOIUrl":"10.1055/s-0044-1785234","url":null,"abstract":"<p><p><b>Introduction</b>  CRISPR-Cas9 gene editing, leveraging bacterial defense mechanisms, offers precise DNA modifications, holding promise in curing genetic diseases. This review critically assesses its potential, analyzing evidence on therapeutic applications, challenges, and future prospects. Examining diverse genetic disorders, it evaluates efficacy, safety, and limitations, emphasizing the need for a thorough understanding among medical professionals and researchers. Acknowledging its transformative impact, a systematic review is crucial for informed decision-making, responsible utilization, and guiding future research to unlock CRISPR-Cas9's full potential in realizing the cure for genetic diseases. <b>Methods</b>  A comprehensive literature search across PubMed, Scopus, and the Web of Science identified studies applying CRISPR-Cas9 gene editing for genetic diseases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria covered in vitro and in vivo models targeting various genetic diseases with reported outcomes on disease modification or potential cure. Quality assessment revealed a generally moderate to high risk of bias. Heterogeneity prevented quantitative meta-analysis, prompting a narrative synthesis of findings. <b>Discussion</b>  CRISPR-Cas9 enables precise gene editing, correcting disease-causing mutations and offering hope for previously incurable genetic conditions. Leveraging inherited epigenetic modifications, it not only fixes mutations but also restores normal gene function and controls gene expression. The transformative potential of CRISPR-Cas9 holds promise for personalized treatments, improving therapeutic outcomes, but ethical considerations and safety concerns must be rigorously addressed to ensure responsible and safe application, especially in germline editing with potential long-term implications.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 1","pages":"113-122"},"PeriodicalIF":1.5,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337123","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":"Patterns of Cytogenomic Findings from a Case Series of Recurrent Pregnancy Loss Provide Insight into the Extent of Genetic Defects Causing Miscarriages.","authors":"Autumn DiAdamo, Hongyan Chai, Mei Ling Chong, Guilin Wang, Jiadi Wen, Yong-Hui Jiang, Peining Li","doi":"10.1055/s-0044-1785227","DOIUrl":"10.1055/s-0044-1785227","url":null,"abstract":"<p><p><b>Background</b>  A retrospective study was performed to evaluate the patterns of cytogenomic findings detected from a case series of products of conception (POC) in recurrent pregnancy loss (RPL) over a 16-year period from 2007 to 2023. <b>Results</b>  This case series of RPL was divided into a single analysis (SA) group of 266 women and a consecutive analysis (CA) group of 225 women with two to three miscarriages analyzed. Of the 269 POC from the SA group and the 469 POC from the CA group, a spectrum of cytogenomic abnormalities of simple aneuploidies, compound aneuploidies, polyploidies, and structural rearrangements/pathogenic copy number variants (pCNVs) were detected in 109 (41%) and 160 cases (34%), five (2%) and 11 cases (2%), 35 (13%) and 36 cases (8%), and 10 (4%) and 19 cases (4%), respectively. Patterns with recurrent normal karyotypes, alternating normal and abnormal karyotypes, and recurrent abnormal karyotypes were detected in 74 (33%), 71 (32%), and 80 (35%) of consecutive miscarriages, respectively. Repeat aneuploidies of monosomy X and trisomy 16, triploidy, and tetraploidy were detected in nine women. <b>Conclusions</b>  A comparable spectrum of cytogenomic abnormalities was noted in the SA and CA groups of RPL. A skewed likelihood of 2/3 for recurrent normal and abnormal karyotypes and 1/3 for alternating normal and abnormal karyotypes in consecutive miscarriages was observed. Routine cytogenetic analysis should be performed for consecutive miscarriages. Further genomic sequencing to search for detrimental and embryonic lethal variants causing miscarriages and pathogenic variants inducing aneuploidies and polyploidies should be considered for RPL with recurrent normal and abnormal karyotypes.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 1","pages":"123-131"},"PeriodicalIF":1.5,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337124","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":"Maternal Uniparental Isodisomy of Chromosome 2 Leading to Homozygous Variants in <i>SPR</i> and <i>ZNF142</i> : A Case Report and Review of the UPD2 Literature.","authors":"Janhawi Kelkar, Miriam DiMaio, Deqiong Ma, Hui Zhang","doi":"10.1055/s-0044-1785442","DOIUrl":"10.1055/s-0044-1785442","url":null,"abstract":"<p><p>We report a 4-year-old girl with neurodevelopmental abnormalities who has maternal uniparental isodisomy of chromosome 2 leading to homozygosity for a likely pathogenic variant in <i>SPR</i> , and a variant of uncertain significance in <i>ZNF142</i> . Biallelic pathogenic variants in <i>SPR</i> lead to sepiapterin reductase deficiency (SRD), a dopa-responsive dystonia. Pathogenic variants in <i>ZNF142</i> are associated with an autosomal recessive neurodevelopmental disorder characterized by impaired speech and hyperkinetic movements, which has significant clinical overlap with SRD. Our patient showed dramatic improvement in motor skills after treatment with levodopa. We also reviewed 67 published reports of uniparental disomy of chromosome 2 (UPD2) associated with various clinical outcomes. These include autosomal recessive disorders associated with loci on chromosome 2, infants with UPD2 whose gestations were associated with confined placental mosaicism for trisomy 2 leading to intrauterine growth restriction with good postnatal catchup growth, and normal phenotypes in children and adults with an incidental finding of either maternal or paternal UPD2. These latter reports provide support for the conclusion that genes located on chromosome 2 are not subject to imprinting. We also explore the mechanisms giving rise to UPD2.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 1","pages":"100-112"},"PeriodicalIF":1.5,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294806","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}