Cold Spring Harbor Molecular Case Studies最新文献

PD-L1⁺ diffuse large B-cell lymphoma with extremely high mutational burden and microsatellite instability due to acquired PMS2 mutation. PD-L1+弥漫大 B 细胞淋巴瘤，因获得性 PMS2 基因突变而具有极高的突变负荷和微卫星不稳定性。

IF 1.8

Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI: 10.1101/mcs.a006318

Andrew W Allbee, James Gerson, Guang Yang, Adam Bagg

引用次数: 0

Novel pathogenic UQCRC2 variants in a female with normal neurodevelopment. 一名神经发育正常的女性的新型致病性UQCRC2变体。

IF 1.8

Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI: 10.1101/mcs.a006295

Lea Abou Haidar, Robert C Harris, Panayotis Pachnis, Hongli Chen, Garrett K Gotway, Min Ni, Ralph J DeBerardinis

{"title":"Novel pathogenic UQCRC2 variants in a female with normal neurodevelopment.","authors":"Lea Abou Haidar, Robert C Harris, Panayotis Pachnis, Hongli Chen, Garrett K Gotway, Min Ni, Ralph J DeBerardinis","doi":"10.1101/mcs.a006295","DOIUrl":"10.1101/mcs.a006295","url":null,"abstract":"Electron transport chain (ETC) disorders are a group of rare, multisystem diseases caused by impaired oxidative phosphorylation and energy production. Deficiencies in complex III (CIII), also known as ubiquinol-cytochrome c reductase, are particularly rare in humans. Ubiquinol-cytochrome c reductase core protein 2 (UQCRC2) encodes a subunit of CIII that plays a crucial role in dimerization. Several pathogenic UQCRC2 variants have been identified in patients presenting with metabolic abnormalities that include lactic acidosis, hyperammonemia, hypoglycemia, and organic aciduria. Almost all previously reported UQCRC2-deficient patients exhibited neurodevelopmental involvement, including developmental delays and structural brain anomalies. Here, we describe a girl who presented at 3 yr of age with lactic acidosis, hyperammonemia, and hypoglycemia but has not shown any evidence of neurodevelopmental dysfunction by age 15. Whole-exome sequencing revealed compound heterozygosity for two novel variants in UQCRC2: c.1189G>A; p.Gly397Arg and c.437T>C; p.Phe146Ser. Here, we discuss the patient's clinical presentation and the likely pathogenicity of these two missense variants.","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10815277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10234223","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}

引用次数: 0

Common clonal origin of three distinct hematopoietic neoplasms in a single patient: B-cell lymphoma, T-cell lymphoma, and polycythemia vera. 一名患者三种不同造血肿瘤的共同克隆起源：B细胞淋巴瘤、T细胞淋巴瘤和红细胞增多症。

IF 1.8

Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI: 10.1101/mcs.a006313

Dingani Nkosi, Andrew W Allbee, Paul G Rothberg, Jonathan W Friedberg, Andrew G Evans

{"title":"Common clonal origin of three distinct hematopoietic neoplasms in a single patient: B-cell lymphoma, T-cell lymphoma, and polycythemia vera.","authors":"Dingani Nkosi, Andrew W Allbee, Paul G Rothberg, Jonathan W Friedberg, Andrew G Evans","doi":"10.1101/mcs.a006313","DOIUrl":"10.1101/mcs.a006313","url":null,"abstract":"The potential for more than one distinct hematolymphoid neoplasm to arise from a common mutated stem or precursor cell has been proposed based on findings in primary human malignancies. Particularly, angioimmunoblastic T-cell lymphoma (AITL), which shares a somatic mutation profile in common with other hematopoietic malignancies, has been reported to occur alongside myeloid neoplasms or clonal B-cell proliferations, with identical mutations occurring in more than one cell lineage. Here we report such a case of an elderly woman who was diagnosed over a period of 8 years with diffuse large B-cell lymphoma, polycythemia vera, and AITL, each harboring identical somatic mutations in multiple genes. Overall, at least five identical nucleotide mutations were shared across multiple specimens, with two identical mutations co-occurring at variable variant allele frequencies in all three specimen types. These findings lend credence to the theory that a common mutated stem cell could give rise to multiple neoplasms through parallel hematopoietic differentiation pathways.","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"9 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10815289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416550","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}

引用次数: 0

De novo TRPM3 missense variant associated with neurodevelopmental delay and manifestations of cerebral palsy. 与神经发育迟缓和脑瘫表现相关的新发TRPM3错义变体。

IF 1.8

Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI: 10.1101/mcs.a006293

Jagadish Chandrabose Sundaramurthi, Anita M Bagley, Hannah Blau, Leigh Carmody, Amy Crandall, Daniel Danis, Michael A Gargano, Anxhela Gjyshi Gustafson, Ellen M Raney, Mallory Shingle, Jon R Davids, Peter N Robinson

引用次数: 0

Novel inherited CDX2 variant segregating in a family with diverse congenital malformations of the genitourinary system. 一个具有多种先天性泌尿生殖系统畸形的家族中分离的新的遗传性CDX2变体。

IF 1.8

Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI: 10.1101/mcs.a006294

Swetha Ramadesikan, Caitlyn M Colwell, Rachel Supinger, Jesse Hunter, Jessica Thomas, Elizabeth Varga, Elaine R Mardis, Richard J Wood, Daniel C Koboldt

{"title":"Novel inherited CDX2 variant segregating in a family with diverse congenital malformations of the genitourinary system.","authors":"Swetha Ramadesikan, Caitlyn M Colwell, Rachel Supinger, Jesse Hunter, Jessica Thomas, Elizabeth Varga, Elaine R Mardis, Richard J Wood, Daniel C Koboldt","doi":"10.1101/mcs.a006294","DOIUrl":"10.1101/mcs.a006294","url":null,"abstract":"Anorectal malformations (ARMs) constitute a group of congenital defects of the gastrointestinal and urogenital systems. They affect males and females, with an estimated worldwide prevalence of 1 in 5000 live births. These malformations are clinically heterogeneous and can be part of a syndromic presentation (syndromic ARM) or as a nonsyndromic entity (nonsyndromic ARM). Despite the well-recognized heritability of nonsyndromic ARM, the genetic etiology in most patients is unknown. In this study, we describe three siblings with diverse congenital anomalies of the genitourinary system, anemia, delayed milestones, and skeletal anomalies. Genome sequencing identified a novel, paternally inherited heterozygous Caudal type Homeobox 2 (CDX2) variant (c.722A > G (p.Glu241Gly)), that was present in all three affected siblings. The variant identified in this family is absent from population databases and predicted to be damaging by most in silico pathogenicity tools. So far, only two other reports implicate variants in CDX2 with ARMs. Remarkably, the individuals described in these studies had similar clinical phenotypes and genetic alterations in CDX2 CDX2 encodes a transcription factor and is considered the master regulator of gastrointestinal development. This variant maps to the homeobox domain of the encoded protein, which is critical for interaction with DNA targets. Our finding provides a potential molecular diagnosis for this family's condition and supports the role of CDX2 in anorectal anomalies. It also highlights the clinical heterogeneity and variable penetrance of ARM predisposition variants, another well-documented phenomenon. Finally, it underscores the diagnostic utility of genomic profiling of ARMs to identify the genetic etiology of these defects.","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10815271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41193559","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}

引用次数: 0

Synchronous T-lymphoblastic lymphoma and neuroblastoma in a 3-yr-old with novel germline SMARCA4 and EZH2 variants. 一例3岁新种系SMARCA4和EZH2变异的同步T淋巴细胞淋巴瘤和神经母细胞瘤。

IF 1.8

Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI: 10.1101/mcs.a006286

Pauline Tibout, Joel Livingston, Nisha Kanwar, Kyoko E Yuki, Adam Shlien, Bo Ngan, Meredith S Irwin, Daniel A Morgenstern, Johann Hitzler, Anita Villani, Sarah Cohen-Gogo

{"title":"Synchronous T-lymphoblastic lymphoma and neuroblastoma in a 3-yr-old with novel germline SMARCA4 and EZH2 variants.","authors":"Pauline Tibout, Joel Livingston, Nisha Kanwar, Kyoko E Yuki, Adam Shlien, Bo Ngan, Meredith S Irwin, Daniel A Morgenstern, Johann Hitzler, Anita Villani, Sarah Cohen-Gogo","doi":"10.1101/mcs.a006286","DOIUrl":"10.1101/mcs.a006286","url":null,"abstract":"T-lymphoblastic lymphoma (T-LLy) is the most common lymphoblastic lymphoma in children and often presents with a mediastinal mass. Lymphomatous suprarenal masses are possible but rare. Here, we discuss the case of a previously healthy 3-yr-old male who presented with mediastinal T-LLy with bilateral suprarenal masses. Following initial treatment, surgical biopsy of persisting adrenal masses revealed bilateral neuroblastoma (NBL). A clinical genetics panel for germline cancer predisposition did not identify any pathogenic variants. Combination large panel (864 genes) profiling analysis in the context of a precision oncology study revealed two novel likely pathogenic heterozygous variants: SMARCA4 c.1420-1G > T p.? and EZH2 c.1943G > C p.(Ile631Phefs*44). Somatic analysis revealed potential second hits/somatic variants in EZH2 (in the T-LLy) and a segmental loss in Chromosome 19p encompassing SMARCA4 (in the NBL). Synchronous cancers, especially at a young age, warrant genetic evaluation for cancer predisposition; enrollment in a precision oncology program assessing germline and tumor DNA can fulfill that purpose, particularly when standard first-line genetic testing is negative and in the setting of tumors that are not classic for common cancer predisposition syndromes.","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10815281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478774","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}

引用次数: 0

Prostate cancer patient stratification by molecular signatures in the Veterans Precision Oncology Data Commons. 退伍军人精确肿瘤数据共享中前列腺癌患者的分子标记分层。

IF 1.8

Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI: 10.1101/mcs.a006298

Kyle M Hernandez, Aarti Venkat, Danne C Elbers, John R Bihn, Mary T Brophy, Nhan V Do, Jennifer La, Qiong Liu, Andrew Prokhorenkov, Noah Metoki-Shlubsky, Feng-Chi Sung, Channing J Paller, Nathanael R Fillmore, Robert L Grossman

{"title":"Prostate cancer patient stratification by molecular signatures in the Veterans Precision Oncology Data Commons.","authors":"Kyle M Hernandez, Aarti Venkat, Danne C Elbers, John R Bihn, Mary T Brophy, Nhan V Do, Jennifer La, Qiong Liu, Andrew Prokhorenkov, Noah Metoki-Shlubsky, Feng-Chi Sung, Channing J Paller, Nathanael R Fillmore, Robert L Grossman","doi":"10.1101/mcs.a006298","DOIUrl":"10.1101/mcs.a006298","url":null,"abstract":"Veterans are at an increased risk for prostate cancer, a disease with extraordinary clinical and molecular heterogeneity, compared with the general population. However, little is known about the underlying molecular heterogeneity within the veteran population and its impact on patient management and treatment. Using clinical and targeted tumor sequencing data from the National Veterans Affairs health system, we conducted a retrospective cohort study on 45 patients with advanced prostate cancer in the Veterans Precision Oncology Data Commons (VPODC), most of whom were metastatic castration-resistant. We characterized the mutational burden in this cohort and conducted unsupervised clustering analysis to stratify patients by molecular alterations. Veterans with prostate cancer exhibited a mutational landscape broadly similar to prior studies, including KMT2A and NOTCH1 mutations associated with neuroendocrine prostate cancer phenotype, previously reported to be enriched in veterans. We also identified several potential novel mutations in PTEN, MSH6, VHL, SMO, and ABL1 Hierarchical clustering analysis revealed two subgroups containing therapeutically targetable molecular features with novel mutational signatures distinct from those reported in the Catalogue of Somatic Mutations in Cancer database. The clustering approach presented in this study can potentially be used to clinically stratify patients based on their distinct mutational profiles and identify actionable somatic mutations for precision oncology.","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10815278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138482093","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}

引用次数: 0

The diagnostic odyssey of a patient with dihydropyrimidinase deficiency: a case report and review of the literature. 二氢嘧啶酶缺乏症患者的诊断奥德赛：病例报告和文献综述。

IF 1.8

Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI: 10.1101/mcs.a006319

Daniah Albokhari, Ohood Alharbi, Alyssa Blesson, Mahim Jain

{"title":"The diagnostic odyssey of a patient with dihydropyrimidinase deficiency: a case report and review of the literature.","authors":"Daniah Albokhari, Ohood Alharbi, Alyssa Blesson, Mahim Jain","doi":"10.1101/mcs.a006319","DOIUrl":"10.1101/mcs.a006319","url":null,"abstract":"Dihydropyrimidinase (DHP) deficiency is an autosomal recessive metabolic disorder caused by biallelic pathogenic variants of DPYS Patients with DHP deficiency exhibit a broad spectrum of phenotypes, ranging from severe neurological and gastrointestinal involvement to cases with no apparent symptoms. The biochemical diagnosis of DHP deficiency is based on the detection of a significant amount of dihydropyrimidines in urine, plasma, and cerebrospinal fluid samples. Molecular genetic testing, specifically the identification of biallelic pathogenic variants in DPYS, has proven instrumental in confirming the diagnosis and facilitating family studies. This case study documents the diagnostic journey of an 18-yr-old patient with DHP deficiency, highlighting features at the severe end of the clinical spectrum. Notably, our patient exhibited previously unreported skeletal features that positively responded to bisphosphonate treatment, contributing valuable insights to the clinical characterization of DHP deficiency. Additionally, a novel DPYS variant was identified and confirmed pathogenicity through metabolic testing, further expanding the variant spectrum of the gene. Our case emphasizes the importance of a comprehensive diagnostic approach using genetic sequencing and metabolic testing for accurate diagnosis.","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"9 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10815279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416552","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}

引用次数: 0

Reclassification of the HPGD p.Ala13Glu variant causing primary hypertrophic osteoarthropathy. 引起原发性肥大性骨关节病的HPGD p.Ala13Glu变体的重新分类。

IF 1.8

Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI: 10.1101/mcs.a006291

Juan J Alban, Alejandra Arango-Ramirez, Jorge A Olave-Rodriguez, Jose A Nastasi-Catanese, Lisa X Rodriguez

引用次数: 0

Pazopanib elicits remarkable response in metastatic porocarcinoma: a functional precision medicine approach. 帕唑帕尼在转移性孔癌中引发显著反应：一种功能精确的医学方法。

IF 1.8

Cold Spring Harbor Molecular Case Studies Pub Date : 2024-01-10 Print Date: 2023-12-01 DOI: 10.1101/mcs.a006308

Sharon Pei Yi Chan, Chen Ee Low, Chun En Yau, Tzu Ping Lin, Weining Wang, Sam Xin Xiu, Po Yin Tang, Baiwen Luo, Nur Fazlin Bte Mohamed Noor, Kristen Alexa Lee, Jianbang Chiang, Tan Boon Toh, Edward Kai-Hua Chow, Valerie Shiwen Yang

{"title":"Pazopanib elicits remarkable response in metastatic porocarcinoma: a functional precision medicine approach.","authors":"Sharon Pei Yi Chan, Chen Ee Low, Chun En Yau, Tzu Ping Lin, Weining Wang, Sam Xin Xiu, Po Yin Tang, Baiwen Luo, Nur Fazlin Bte Mohamed Noor, Kristen Alexa Lee, Jianbang Chiang, Tan Boon Toh, Edward Kai-Hua Chow, Valerie Shiwen Yang","doi":"10.1101/mcs.a006308","DOIUrl":"10.1101/mcs.a006308","url":null,"abstract":"Metastatic porocarcinomas (PCs) are vanishingly rare, highly aggressive skin adnexal tumors with mortality rates exceeding 70%. Their rarity has precluded the understanding of their disease pathogenesis, let alone the conduct of clinical trials to evaluate treatment strategies. There are no effective agents for unresectable PCs. Here, we successfully demonstrate how functional precision medicine was implemented in the clinic for a metastatic PC with no known systemic treatment options. Comprehensive genomic profiling of the tumor specimen did not yield any actionable genomic aberrations. However, ex vivo drug testing predicted pazopanib efficacy, and indeed, administration of pazopanib elicited remarkable clinicoradiological response. Pazopanib and its class of drugs should be evaluated for efficacy in other cases of PC, and the rationale for efficacy should be determined when PC tumor models become available. A functional precision medicine approach could be useful to derive effective treatment options for rare cancers.","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10815280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013653","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}

引用次数: 0