Cold Spring Harbor Molecular Case Studies最新文献

{"title":"Progressive metastatic infantile fibrosarcoma with multiple acquired mutations.","authors":"Larissa V Furtado,&nbsp;Marija Kacar,&nbsp;Roya Mostafavi,&nbsp;Zonggao Shi,&nbsp;Robert Ruiz,&nbsp;Selene C Koo,&nbsp;Teresa Santiago,&nbsp;Blair Segers,&nbsp;Matthew J Krasin,&nbsp;Zachary R Abramson,&nbsp;Barry Shulkin,&nbsp;Lindsay J Talbot,&nbsp;Alberto Pappo,&nbsp;Jessica Gartrell","doi":"10.1101/mcs.a006277","DOIUrl":"https://doi.org/10.1101/mcs.a006277","url":null,"abstract":"<p><p>Infantile fibrosarcoma is the most common soft-tissue sarcoma in children under the age of 1 yr and is defined molecularly by <i>NTRK</i> fusion proteins. This tumor is known to be locally invasive; however, although rare, metastases can occur. The <i>NTRK</i> fusion acts as a driver for tumor formation, which can be targeted by first- and second-generation <i>TRK</i> inhibitors. Although <i>NTRK</i> gatekeeper mutations have been well-described as mechanisms of resistance to these agents, alternative pathway mutations are rare. Here, we report the case of a patient with infantile fibrosarcoma treated with chemotherapy and <i>TRK</i> inhibition that developed metastatic, progressive disease with multiple acquired mutations, including <i>TP53</i>, <i>SUFU</i>, and an <i>NTRK</i> F617L gatekeeper mutation. Alterations in pathways of <i>SUFU</i> and <i>TP53</i> have been widely described in the literature in other tumors; however, not yet in infantile fibrosarcoma. Although most patients have a sustained response to <i>TRK</i> inhibitors, a subset will go on to develop mechanisms of resistance that have implications for clinical management, such as in our patient. We hypothesize this constellation of mutations contributed to the patient's aggressive clinical course. Taken together, we report the first case of infantile fibrosarcoma with <i>ETV6::NTRK3</i> and acquired <i>SUFU</i>, <i>TP53</i>, and <i>NTRK</i> F617L gatekeeper mutation along with detailed clinical course and management. Our report highlights the importance of genomic profiling in recurrent infantile fibrosarcoma to reveal actionable mutations, such as gatekeeper mutations, that can improve patient outcomes.</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"9 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e4/0e/MCS006277Fur.PMC10240842.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9937727","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":"Complete response to chemoimmunotherapy with bevacizumab in synchronous multiple primary cancers: pulmonary adenocarcinoma and sarcomatoid carcinoma.","authors":"Diogo Garcia,&nbsp;Isa Mambetsariev,&nbsp;Jeremy Fricke,&nbsp;Daniel Schmolze,&nbsp;Michelle Afkhami,&nbsp;Rifat Mannan,&nbsp;Pauline Kim,&nbsp;Shaira Therese Dingal,&nbsp;Bao Nguyen,&nbsp;Razmig Babikian,&nbsp;Yuman Fong,&nbsp;Ravi Salgia","doi":"10.1101/mcs.a006262","DOIUrl":"https://doi.org/10.1101/mcs.a006262","url":null,"abstract":"<p><p>A small percentage of patients have multiple synchronous primary cancers at presentation. In the last five years, many regimens associated with immunotherapy and chemotherapy were approved for first-line metastatic non-small-cell lung cancer (NSCLC) and other solid tumors, but the study of immunotherapy when multiple cancers are present in one patient remains incomplete. Next-generation sequencing biomarkers and immunotherapy markers including PD-L1 can be effectively utilized in the diagnosis and treatment plan for multiple synchronous primary cancers. Immune biomarkers and PD-L1 expression warrant individualized treatments in synchronous primary adenocarcinoma and pulmonary sarcomatoid carcinoma. We describe the case of a patient with pulmonary sarcomatoid carcinoma and lung adenocarcinoma, metastatic to brain de novo. The patient achieved a complete response after only three cycles of carboplatin, paclitaxel, bevacizumab, and atezolizumab and remains free of any evidence of disease after 18 mo of maintenance therapy.</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"9 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b2/47/MCS006262Gar.PMC10240843.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9635784","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":"<i>PIK3CA</i> copy-number gain and inhibitors of the PI3K/AKT/mTOR pathway in triple-negative breast cancer.","authors":"Ottavia Amato,&nbsp;Laurence Buisseret,&nbsp;Geraldine Gebhart,&nbsp;Nicolas Plouznikoff,&nbsp;Denis Larsimont,&nbsp;Ahmad Awada,&nbsp;Martine Piccart,&nbsp;Philippe Aftimos","doi":"10.1101/mcs.a006255","DOIUrl":"https://doi.org/10.1101/mcs.a006255","url":null,"abstract":"<p><p>As wider insights are gained on the molecular landscape of triple-negative breast cancer (TNBC), novel targeted therapeutic strategies might become an option in this setting as well. Activating mutations of <i>PIK3CA</i> represent the second most common alteration in TNBC after the <i>TP53</i> mutation, with a prevalence of ∼10%-15%. Considering the well-established predictive role of <i>PIK3CA</i> mutations for response to agents targeting the PI3K/AKT/mTOR pathway, several clinical trials are currently evaluating these drugs in patients with advanced TNBC. However, much less is known regarding the actionability of <i>PIK3CA</i> copy-number gains, which represent a thoroughly common molecular alteration in TNBC, with a prevalence estimated at 6%-20%, and are listed as \"likely gain-of-function\" alterations in the OncoKB database. In the present paper, we describe two clinical cases in which patients harboring <i>PIK3CA</i>-amplified TNBC received a targeted treatment with the mTOR-inhibitor everolimus and the PI3K-inhibitor alpelisib, respectively, with evidence of disease response on 18F-FDG positron-emission tomography (PET) imaging. Hence, we discuss the evidence presently available regarding a possible predictive value of <i>PIK3CA</i> amplification for response to targeted treatment strategies, suggesting that this molecular alteration might represent an intriguing biomarker in this sense. Considering that few of the currently active clinical trials assessing agents targeting the PI3K/AKT/mTOR pathway in TNBC select patients based on tumor molecular characterization, and none of these based on <i>PIK3CA</i> copy-number status, we urge for the introduction of <i>PIK3CA</i> amplification as a criterion for patient selection in future clinical trials in this setting.</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"9 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/25/fb/MCS006255Ama.PMC10240844.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9634766","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":"Single-cell profiling of multiple myeloma reveals molecular response to FGFR3 inhibitor despite clinical progression.","authors":"Danielle C Croucher,&nbsp;Anup Joseph Devasia,&nbsp;Dor D Abelman,&nbsp;Ali Mahdipour-Shirayeh,&nbsp;Zhihua Li,&nbsp;Natalie Erdmann,&nbsp;Rodger Tiedemann,&nbsp;Trevor J Pugh,&nbsp;Suzanne Trudel","doi":"10.1101/mcs.a006249","DOIUrl":"https://doi.org/10.1101/mcs.a006249","url":null,"abstract":"<p><p>Genomic characterization of cancer has enabled identification of numerous molecular targets, which has led to significant advances in personalized medicine. However, with few exceptions, precision medicine approaches in the plasma cell malignancy multiple myeloma (MM) have had limited success, likely owing to the subclonal nature of molecular targets in this disease. Targeted therapies against FGFR3 have been under development for the past decade in the hopes of targeting aberrant FGFR3 activity in MM. FGFR3 activation results from the recurrent transforming event of t(4;14) found in ∼15% of MM patients, as well as secondary <i>FGFR3</i> mutations in this subgroup. To evaluate the effectiveness of targeting FGFR3 in MM, we undertook a phase 2 clinical trial evaluating the small-molecule FGFR1-4 inhibitor, erdafitinib, in relapsed/refractory myeloma patients with or without <i>FGFR3</i> mutations (NCT02952573). Herein, we report on a single t(4;14) patient enrolled on this study who was identified to have a subclonal <i>FGFR3</i> stop-loss deletion. Although this individual eventually progressed on study and succumbed to their disease, the intended molecular response was revealed through an extensive molecular characterization of the patient's tumor at baseline and on treatment using single-cell genomics. We identified elimination of the <i>FGFR3</i>-mutant subclone after treatment and expansion of a preexisting clone with loss of Chromosome 17p. Altogether, our study highlights the utility of single-cell genomics in targeted trials as they can reveal molecular mechanisms that underlie sensitivity and resistance. This in turn can guide more personalized and targeted therapeutic approaches, including those that involve FGFR3-targeting therapies.</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"9 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7c/1e/MCS006249Cro.PMC10240837.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10125744","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":"Milder presentation of osteogenesis imperfecta type VIII due to compound heterozygosity for a predicted loss-of-function variant and novel missense variant in <i>P3H1</i>-further expansion of the phenotypic spectrum.","authors":"Kristen A Mikhail,&nbsp;Elizabeth VanSickle,&nbsp;Linda Z Rossetti","doi":"10.1101/mcs.a006260","DOIUrl":"https://doi.org/10.1101/mcs.a006260","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) is a heritable disorder of bone metabolism characterized by multiple fractures with minimal trauma. Autosomal recessive OI type VIII is associated with biallelic pathogenic variants in <i>P3H1</i> and classically characterized by skeletal anomalies in addition to significant bone fragility, sometimes presenting with in utero fractures and/or neonatal lethality. <i>P3H1</i> encodes a collagen prolyl hydroxylase that critically 3-hydroxylates proline residue 986 on the α chain of collagen types I and II to achieve proper folding and assembly of mature collagen and is present in a complex with CRTAP and CypB. Most individuals with OI type VIII have had biallelic predicted loss-of-function variants leading to reduced or absent levels of <i>P3H1</i> mRNA. The reported missense variants have all fallen in the catalytic domain of the protein and are thought to be associated with a milder phenotype. Here, we describe an infant presenting with five long bone fractures in the first year of life found to have a novel missense variant in <i>trans</i> with a nonsense variant in <i>P3H1</i> without any other bony anomalies on imaging. We hypothesize that missense variants in the catalytic domain of P3H1 lead to decreased but not absent hydroxylation of Pro986, with preserved KDEL retention signal and complex stability, causing an attenuated phenotype.</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"9 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/2a/MCS006260Mik.PMC10111797.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9444566","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 novel <i>WFS1</i> variant associated with isolated congenital cataracts.","authors":"Angela Krutish,&nbsp;James Elmore,&nbsp;Werner Ilse,&nbsp;Janine L Johnston,&nbsp;Dustin Hittel,&nbsp;Marina Kerr,&nbsp;Aneal Khan,&nbsp;Cheryl Rockman-Greenberg,&nbsp;Aizeddin A Mhanni","doi":"10.1101/mcs.a006259","DOIUrl":"https://doi.org/10.1101/mcs.a006259","url":null,"abstract":"<p><p>Biallelic variants in the <i>WFS1</i> gene are associated with Wolfram syndrome. However, recent publications document that heterozygous variants can lead to a variety of phenotypes, such as Wolfram-like syndrome or isolated features of Wolfram syndrome. In this case report, we present a male patient with a history of congenital cataracts and subjective complaints of muscle weakness. Clinical assessment demonstrated normal muscle strength, and genomic, biochemical, electrophysiologic, and muscle biopsy studies did not identify a potential cause of the proband's perceived muscle weakness. Whole-exome sequencing identified a novel de novo variant in the <i>WFS1</i> gene (c.1243G > T), representing one of only several patients in the published literature with isolated congenital cataracts and a heterozygous <i>WFS1</i> variant. The variety of phenotypes associated with heterozygous variants in <i>WFS1</i> suggests that this gene should be considered as a cause of both dominant and biallelic/recessive forms of disease. Future research should focus on elucidating the mechanism(s) of disease and variable expressivity in <i>WFS1</i> in order to improve our ability to provide patients and families with anticipatory guidance about the disease, including appropriate screening and medical interventions.</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"9 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/49/da/MCS006259Kru.PMC10111794.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9446290","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 <i>TRIP11:: FLT3</i> gene fusion in a patient with myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase gene fusions: a case report and review of the literature.","authors":"Elise R Venable,&nbsp;Marie-France Gagnon,&nbsp;Beth A Pitel,&nbsp;Jeanne M Palmer,&nbsp;Jess F Peterson,&nbsp;Linda B Baughn,&nbsp;Nicole L Hoppman,&nbsp;Patricia T Greipp,&nbsp;Rhett P Ketterling,&nbsp;Mrinal S Patnaik,&nbsp;Katalin Kelemen,&nbsp;Xinjie Xu","doi":"10.1101/mcs.a006243","DOIUrl":"https://doi.org/10.1101/mcs.a006243","url":null,"abstract":"<p><p>Myeloid/lymphoid neoplasms with <i>FLT3</i> gene fusions have recently been included among myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) in the World Health Organization classification and International Consensus Classification. As this entity remains remarkably rare, its scope and phenotypic features are evolving. In this report, we describe a 33-yr-old male with MLN-TK. Conventional chromosome analysis revealed a t(13;14)(q12;q32). Further analysis with mate-pair sequencing (MPseq) confirmed a <i>TRIP11::FLT3</i> gene fusion. A diagnosis of MLN-TK was rendered. To the best of our knowledge, we report the third case of MLN-TK with a <i>TRIP11::FLT3</i> gene fusion. In contrast to previously described cases, our case exhibited distinctly mild clinical features and disease behavior, emphasizing the diverse spectrum of MLN-TK at primary presentation and variability in disease course. MLN-TK with <i>FLT3</i> gene fusions are a genetically defined entity which may be targetable with tyrosine kinase inhibitors with anti-FLT3 activity. Accordingly, from diagnostic and therapeutic viewpoints, genetic testing for <i>FLT3</i> rearrangements using fluorescence in situ hybridization (FISH) or sequencing-based assays should be pursued for patients with chronic eosinophilia.</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"9 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/51/24/MCS006243Ven.PMC10111796.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9814903","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":"Genomic profile of two Brazilian choroid plexus tumors by whole-exome sequencing.","authors":"Felipe Antonio de Oliveira Garcia,&nbsp;Adriane Feijó Evangelista,&nbsp;Bruna Minniti Mançano,&nbsp;Daniel Antunes Moreno,&nbsp;Gustavo Noriz Berardinelli,&nbsp;Flávia Escremim de Paula,&nbsp;Augusto Perazzolo Antoniazzi,&nbsp;Carlos Almeida Júnior,&nbsp;Ismael Lombardi,&nbsp;Iara Santana,&nbsp;Gustavo Ramos Teixeira,&nbsp;Caio Evangelista Costa,&nbsp;Rui Manuel Reis","doi":"10.1101/mcs.a006245","DOIUrl":"https://doi.org/10.1101/mcs.a006245","url":null,"abstract":"<p><p>Choroid plexus tumors (CPTs) are rare intracranial neoplasms, representing <1% of all brain tumors, yet they represent 20% of first-year pediatric brain tumors. Although these tumors have been linked to <i>TP53</i> germline mutations in the context of Li-Fraumeni syndrome, their somatic driver alterations remain poorly understood. In this study, we report two cases of lateral ventricle tumors: 3-yr-old male diagnosed with an atypical choroid plexus papilloma (aCPP), and a 6-mo-old female diagnosed with a choroid plexus carcinoma (CPC). We performed whole-exome sequencing of paired blood and tumor tissue in both patients, categorized somatic variants, and determined copy-number alterations. Our analysis revealed a tier II variant (Association for Molecular Pathology [AMP] criteria) in <i>BRD1,</i> a <i>H3</i> and <i>TP53</i> acetylation agent, in the aCPP. In addition, we detected copy-number gains on Chromosomes 12, 18, and 20 and copy-number losses on Chromosomes 13q and 22q (<i>BRD1</i> locus) in this tumor. The CPC tumor had only a pathogenic germline <i>TP53</i> variant, based on American College of Medical Genetics (ACMG) criteria, with a clinical and familiar history of Li-Fraumeni syndrome. The CPC patient presented loss of heterozygosity (LoH) of <i>TP53</i> loci and hyperdiploid genome. Both tumors were microsatellite-stable. This is the first study performing whole-exome sequencing in Brazilian choroid plexus tumors, and in line with the literature, we corroborate the absence of recurrent somatic mutations in these tumors. Further studies with larger sample sizes are necessary to confirm our findings and better understand the underlying biology of these tumors.</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"9 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/01/a1/MCS006245Gar.PMC10111795.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9444569","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":"Case report: olaparib use in metastatic lung adenocarcinoma with <i>BRCA2</i> pathogenic variant.","authors":"Jonathan Soon Jian Hao, Chan Sock Hoai, Daniel Tan Shao Weng, Joanne Ngeow, Jianbang Chiang","doi":"10.1101/mcs.a006223","DOIUrl":"10.1101/mcs.a006223","url":null,"abstract":"<p><p>Poly (ADP-ribose) polymerase (PARP) inhibitors have been approved in malignancies associated with germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variants, such as breast, ovarian, prostate, and pancreatic cancer. In malignancies not associated with germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variants, the therapeutic relevance of PARP inhibitors is less clear. Non-small-cell lung cancer (NSCLC) is known to demonstrate somatic alterations in <i>BRCA1</i> or <i>BRCA2</i> gene. The current report is on a gentleman with metastatic lung adenocarcinoma with a somatic <i>BRCA2</i> pathogenic variant, who was effectively treated with olaparib. Furthermore, we discuss the existing data for use of PARP inhibitors in NSCLC. This study highlights the utility of next-generation sequencing in identifying gene mutations and demonstrates how such information can be used to select targeted therapies in patients with actionable molecular alterations.</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"8 7","pages":""},"PeriodicalIF":1.8,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9808557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10634744","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":"Rapid genome sequencing identifies novel variants in complement factor I.","authors":"Katherine M Rodriguez, Jordan Vaught, Michelle Dilley, Kataryzna Ellsworth, Alaina Heinen, Edsel M Abud, Yuzhou Zhang, Richard J H Smith, Robert Sheets, Bob Geng, Hal M Hoffman, H Michael Worthen, David Dimmock, Nicole G Coufal","doi":"10.1101/mcs.a006239","DOIUrl":"10.1101/mcs.a006239","url":null,"abstract":"<p><p>Complement factor I deficiency (CFID; OMIM #610984) is a rare immunodeficiency caused by deficiencies in the serine protease complement factor I (CFI). CFID is characterized by predisposition to severe pneumococcal infection, often in infancy. We report a previously healthy adolescent male who presented with respiratory failure secondary to pneumococcal pneumonia and severe systemic inflammatory response. Rapid genome sequencing (rGS) identified compound heterozygous variants in <i>CFI</i> in the proband, with a novel maternally inherited likely pathogenic variant, a single nucleotide deletion resulting in premature stop (c.1646del; p.Asn549ThrfsTer25) and a paternally inherited novel likely pathogenic deletion (Chr 4:110685580-110692197del).</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":"8 7","pages":""},"PeriodicalIF":1.8,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/aa/be/MCS006239Rod.PMC9808552.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10634745","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}