112,117 results match your criteria mutations cases


LDLR variants functional characterization: Contribution to variant classification.

Atherosclerosis 2021 Jun 10;329:14-21. Epub 2021 Jun 10.

Unidade de I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal; BioISI - Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal. Electronic address:

Background And Aims: Familial hypercholesterolaemia (FH) is an autosomal disorder of lipid metabolism presenting with increased cardiovascular risk. LDLR mutations are the cause of disease in 90% of the cases but functional studies have only been performed for about 15% of all LDLR variants. In the Portuguese Familial Hypercholesterolemia Study (PFHS), 142 unique LDLR alterations were identified and 44 (30%) lack functional characterization. Read More

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Incidence and Prognosis of Clonal Hematopoiesis in patients with Chronic Idiopathic Neutropenia.

Blood 2021 Jun 24. Epub 2021 Jun 24.

University of Pavia, Italy.

The incidence and prognosis of clonal hematopoiesis in patients with isolated neutropenia among patients with idiopathic cytopenia of undetermined significance (ICUS), known as ICUS-N or chronic idiopathic neutropenia (CIN) patients, is poorly defined. In the present study we sought to investigate the frequency and clinical significance of mutations of genes implicated in myeloid malignancies using next generation sequencing, in CIN patients (n=185) with a long follow-up. We found that 21/185 patients (11. Read More

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Large Ovarian Follicle Cyst: Benign Mimic of Cystic Adult Granulosa Cell Tumor.

Int J Gynecol Pathol 2021 Jun 23. Epub 2021 Jun 23.

Department of Pathology (E.R.M.M., T.H., S.L.S.) Rogel Cancer Center (S.L.S.), University of Michigan, Ann Arbor, Michigan.

While most ovarian follicle cysts are <8 cm in greatest dimension, much larger follicle cysts (up to 18.5 cm) have been reported. To our knowledge, the FOXL2 mutation status of such cases has not been documented in the literature. Read More

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Germline RUNX1 variation and predisposition to childhood acute lymphoblastic leukemia.

J Clin Invest 2021 Jun 24. Epub 2021 Jun 24.

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, United States of America.

Genetic alterations in the RUNX1 gene are associated with benign and malignant blood disorders, particularly of megakaryocyte and myeloid lineages. The role of RUNX1 in acute lymphoblastic leukemia (ALL) is less clear, particularly how germline genetic variation influences the predisposition to this type of leukemia. Sequencing 4,836 children with B-ALL and 1,354 cases of T-ALL, we identified 31 and 18 germline RUNX1 variants, respectively. Read More

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Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium.

J Clin Oncol 2021 Jun 24:JCO2003060. Epub 2021 Jun 24.

Department of Pediatrics, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.

Purpose: Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor, and beyond fusion status, no genomic markers are available for risk stratification. We present an international consortium study designed to determine the incidence of driver mutations and their association with clinical outcome. Read More

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H3K27me3 immunostaining is diagnostic and prognostic in diffuse gliomas with oligodendroglial or mixed oligoastrocytic morphology.

Virchows Arch 2021 Jun 24. Epub 2021 Jun 24.

Department of Diagnostics and Public Health, Section of Anatomic Pathology, University of Verona, Policlinico G.B. Rossi. P.le L.A. Scuro 10, 37134, Verona, Italy.

Oligodendroglioma is defined by IDH mutation and 1p/19q codeletion. The latter is mutually exclusive to ATRX immunohistochemical loss and has been recently associated with the loss of H3K27me3 immunostaining. We aimed to assess the diagnostic and prognostic value of H3K27me3 immuno-expression in diffuse gliomas with oligodendroglial or mixed oligoastrocytic morphology. Read More

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Skull Base Tumors: Neuropathology and Clinical implications.

Neurosurgery 2021 Jun 23. Epub 2021 Jun 23.

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Tumors that arise in and around the skull base comprise a wide range of common and rare entities. Recent studies have advanced our understanding of their pathogenesis, which in some cases, have significantly influenced clinical practice. The genotype of meningiomas is strongly associated with their phenotype, including histologic subtype and tumor location, and clinical outcome. Read More

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Dissecting Clonal Hematopoiesis in Tissues of Classical Hodgkin Lymphoma Patients.

Blood Cancer Discov 2021 May 10;2(3):216-225. Epub 2021 Apr 10.

Institute of Hematology and Center for Hemato-Oncology Research, University and Hospital of Perugia - Italy.

Clonal hematopoiesis predisposes to hematological malignancies. However, clonal hematopoiesis is understudied in classical Hodgkin lymphoma (cHL), a mature B-cell neoplasm exhibiting the most abundant microenvironment. We analyzed clonal hematopoiesis in 40 cHL cases by sequencing microdissected tumor cells and matched normal cells from blood and/or lymph nodes. Read More

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The role of HCFC1 in syndromic and non-syndromic intellectual disability.

Med Res Arch 2020 Jun 18;8(6). Epub 2020 Jun 18.

Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968.

Mutations in the gene are associated with cases of syndromic () and non-syndromic intellectual disability. Syndromic individuals present with severe neurological defects including intractable epilepsy, facial dysmorphia, and intellectual disability. Non-syndromic individuals have also been described and implicate a role for HCFC1 during brain development. Read More

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Case Report: Two Chinese Infants of Sengers Syndrome Caused by Mutations in Gene.

Front Pediatr 2021 7;9:639687. Epub 2021 Jun 7.

Heart Center, Qingdao Women and Children's Hospital, Affiliated to Qingdao University, Qingdao, China.

Sengers syndrome (OMIM #212350) is a rare autosomal recessive disorder due to mutations in acylglycerol kinase () gene. We report two cases that were diagnosed clinically and confirmed genetically. Both infants had typical clinical features characterized by hypertrophic cardiomyopathy, bilateral cataracts, myopathy, and lactic acidosis, and heart failure was the most severe manifestation. Read More

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Whole-exon sequencing insights into pancreatic synovial sarcoma: a case report.

Gland Surg 2021 May;10(5):1812-1818

Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.

More than 30 cases of synovial sarcoma are sequenced on all organs of cBioPortal database, but it has not yet been reported before. Here, we reported a case of a 66-year-old male patient with an upper abdominal pain for half a month and a previous history of oral cancer. During this hospitalization, the patient underwent laparoscopic exploration followed by open pancreaticoduodenectomy. Read More

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Complete disease remission in a and co-mutated brain oligometastatic lung cancer patient after immuno-chemotherapy and surgical resection: a case report.

Transl Lung Cancer Res 2021 May;10(5):2298-2305

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Lung cancer is the most common primary malignancy and tends to metastasize to the brain. A multimodal approach, including systematic therapy (targeted therapy, chemotherapy, immunotherapy) and local consolidative therapy (surgical intervention, radiation therapy, ablation therapy), is essential for treatment of oligometastatic lung cancer. The systemic immunotherapy has been shown to increase response rate and survival, which then has the potential benefit of making localized treatment more feasible for some cases of oligometastatic cancer. Read More

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Liquid biopsy in non-small cell lung cancer-current status and future outlook-a narrative review.

Transl Lung Cancer Res 2021 May;10(5):2237-2251

Department of Thoracic Surgery, Medical University of Graz, Graz, Austria.

Lung cancer ranks first as the cause of cancer-associated deaths gobally. The American Cancer Society estimates for 228,820 new cases and 135,720 deaths from lung cancer in the United States for the year 2020. Targeted treatment options have rapidly emerged for non-small cell lung cancer (NSCLC) within the past decade. Read More

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Earlier extracranial progression and shorter survival in ALK-rearranged lung cancer with positive liquid rebiopsies.

Transl Lung Cancer Res 2021 May;10(5):2118-2131

Division of Cancer Genome Research, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Background: Liquid rebiopsies can detect resistance mutations to guide therapy of anaplastic lymphoma kinase-rearranged (ALK) non-small-cell lung cancer (NSCLC) failing tyrosine kinase inhibitors (TKI). Here, we analyze how their results relate to the anatomical pattern of disease progression and patient outcome.

Methods: Clinical, molecular, and radiologic characteristics of consecutive TKI-treated ALK NSCLC patients were analyzed using prospectively collected plasma samples and the 17-gene targeted AVENIO kit, which covers oncogenic drivers and all exons. Read More

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A Rare Case of Small Cell Lung Cancer With an Epidermal Growth Factor Receptor Mutation and Its Response to Osimertinib.

Cureus 2021 May 20;13(5):e15136. Epub 2021 May 20.

Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, Queens Hospital Center, New York City, USA.

Small cell lung cancer (SCLC) accounts for less than 15% of the cases of lung cancer. Epidermal growth factor receptor (EGFR) mutations are rarely reported in association with SCLC. EGFR tyrosine kinase inhibitors (TKI) are approved as the first-line therapy for metastatic non-small cell lung cancer (NSCLC). Read More

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An intronic variant disrupts mRNA splicing and causes -related skeletal dysplasia.

J Pediatr Endocrinol Metab 2021 Jun 23. Epub 2021 Jun 23.

Department of Pediatric Endocrinology and Genetics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute for Pediatric Research, Shanghai, China.

Objectives: Achondroplasia and hypochondroplasia are the most common forms of disproportionate short stature, of which the vast majority of cases can be attributed to the hotspot missense mutations in the gene . Here we presented cases with a novel cryptic splicing variant of gene and aimed to interrogate the variant pathogenicity.

Case Presentaiton: In whole exome sequencing of two patients with hypochondroplasia-like features, a intronic variant c. Read More

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Molecular and clinical findings of Turkish patients with hereditary fructose intolerance.

J Pediatr Endocrinol Metab 2021 Jun 23. Epub 2021 Jun 23.

Ankara Yıldırım Beyazıt University, Ankara City Hospital, Ankara, Turkey.

Objectives: Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by a deficiency in aldolase B that can result in hypoglycemia, nausea, vomiting, abdominal pain, liver and kidney dysfunction, coma, and even death. This study aims to represent the clinical features and molecular genetic analysis data of the patients diagnosed with HFI in our study population.

Methods: The medical records of the 26 patients with HFI were evaluated retrospectively. Read More

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MAN1B1-CDG: novel patients and novel variant.

J Pediatr Endocrinol Metab 2021 Jun 23. Epub 2021 Jun 23.

Department of Pediatrics, Center for Metabolic Diseases, KU Leuven, Leuven, Belgium.

Objectives: Congenital disorders of glycosylation (CDGs) are a group of genetic disorders due to hypoglycosylation of proteins and lipids. A type I pattern is associated with defects in glycan assembly and transfer (CDG-I; cytosol; and endoplasmic reticulum defects), a type II pattern is seen in processing defects of the Golgi apparatus. MAN1B1-CDG is an autosomal recessive CDG-II due to mutations in the 1,2-mannosidase gene (MAN1B1), mainly characterized by psychomotor disability, facial dysmorphism, truncal obesity, and hypotonia. Read More

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Thymic carcinoma with Lynch syndrome or microsatellite instability, a rare entity responsive to immunotherapy.

Eur J Cancer 2021 Jun 20;153:162-167. Epub 2021 Jun 20.

Division of Medical Oncology for Melanoma & Sarcoma, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Importance: Thymic carcinoma (TC) is a rare aggressive tumour occurring in adults characterised by one of the lowest tumor mutational burdens (TMB). Microsatellite instability (MSI) is a mutational signature, caused by defects in the DNA MisMatch Repair (MMR) system, that predicts benefit from immunotherapy and causes high TMB. Fragmentary and unstructured evidence of these conditions co-occurring are reported in literature. Read More

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SLC35A2-CDG: novel variants with two ends of the spectrum.

J Pediatr Endocrinol Metab 2021 Jun 21. Epub 2021 Jun 21.

Department of Pediatric Neurology, Ankara, Turkey.

Objectives: Congenital disorders of glycosylation (CDGs) are rare inherited metabolic disorders associated with facial dysmorphism and in the majority of the patients, there is an important neurological impairment. Epilepsy was a main concern in rare forms of the disease. There are two groups of the disease: CDG-I results from the defects in glycan addition to the N-terminal and CDG-II occurs due to defects in the processing of protein bound glycans. Read More

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High Rates of Ultraviolet-Signature Mutations in Squamous Cell Carcinomas of the Parotid Gland and Prognostic Implications.

Head Neck Pathol 2021 Jun 23. Epub 2021 Jun 23.

Department of Pathology (Anatomic Pathology), The University of Chicago Medicine, Chicago, USA.

In the absence of clear pathologic differences, clinical history may differentiate potential primary parotid squamous cell carcinomas (SCC) from metastases. The presence of an ultraviolet (UV) signature can distinguish between tumors of cutaneous and non-cutaneous origin. This study aimed to investigate rates of UV signature mutations in squamous cell carcinomas of the parotid gland as well as differences in clinical features between tumors of cutaneous and non-cutaneous origin. Read More

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Biallelic ADGRV1 variants are associated with Rolandic epilepsy.

Neurol Sci 2021 Jun 23. Epub 2021 Jun 23.

Department of Pediatrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, 11 Renminxi Road 11, Foshan, 528000, Guangdong, China.

Objective: Rolandic epilepsy (RE) is among the most common focal epilepsies in childhood. For the majority of patients with RE and atypical RE (ARE), the etiology remains elusive. We thus screened patients with RE/ARE in order to detect disease-causing variants. Read More

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Prevalence and clinical significance of occult hepatitis B infection in The Gambia, West Africa.

J Infect Dis 2021 Jun 23. Epub 2021 Jun 23.

Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, UK.

Background: Prevalence of occult hepatitis B infection (OBI) and its clinical outcomes have been poorly studied in Africa.

Method: Using the PROLIFICA cohort, we compared the prevalence of OBI between HBsAg-negative healthy adults screened from the general population (controls) and HBsAg-negative patients with advanced liver disease (cases) and estimated the population attributable fraction for the effect of OBI on advanced liver disease.

Results: OBI prevalence was significantly higher among the cases (15/82, 18. Read More

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Is neutrophilic dermatosis a manifestation of familial Mediterranean fever?

Scand J Rheumatol 2021 Jun 23:1-8. Epub 2021 Jun 23.

Internal Medicine Department, Reference Centre for Autoinflammatory Diseases and Amyloidosis (CEREMAIA), Tenon Hospital, Paris, France.

: Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disease. It is associated with mutations. Its main features are recurrent episodes of fever and serositis. Read More

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Computer-assisted image analysis of cytological specimens clarify the correlation between nuclear size and intranuclear cytoplasmic inclusions regardless of BRAFV600E mutation in papillary thyroid carcinoma.

Cytopathology 2021 Jun 22. Epub 2021 Jun 22.

Laboratory of Histopathology and Cytopathology, Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, Japan.

Objective: The morphological features of nuclei in cytological and histological specimens were compared and examined for the presence of BRAFV600E mutation and the appearance rate of intranuclear cytoplasmic inclusion (NI).

Methods: BRAFV600E mutation was identified using a mutation-specific antibody (clone; VE1) in 103 thyroid papillary carcinoma cases at Gunma University Hospital. The nuclear area, perimeter, and roundness of the corresponding cytological specimens and hematoxylin and eosin-stained specimens were analyzed using image analysis software, and the appearance rate of NI was calculated and compared. Read More

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Tracking SARS-CoV-2 Spike Protein Mutations in the United States (2020/01 - 2021/03) Using a Statistical Learning Strategy.

bioRxiv 2021 Jun 15. Epub 2021 Jun 15.

The emergence and establishment of SARS-CoV-2 variants of interest (VOI) and variants of concern (VOC) highlight the importance of genomic surveillance. We propose a statistical learning strategy (SLS) for identifying and spatiotemporally tracking potentially relevant Spike protein mutations. We analyzed 167,893 Spike protein sequences from US COVID-19 cases (excluding 21,391 sequences from VOI/VOC strains) deposited at GISAID from January 19, 2020 to March 15, 2021. Read More

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Parafibromin Abnormalities in Ossifying Fibroma.

J Endocr Soc 2021 Jul 8;5(7):bvab087. Epub 2021 May 8.

Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, CT 06030, USA.

Ossifying fibromas are very rare tumors that are sometimes seen as part of the hyperparathyroidism-jaw tumor syndrome (HPT-JT), which is caused by inactivating mutations of the tumor suppressor gene mutations have been identified in a subset of sporadic cases but aberrant expression of the encoded protein, parafibromin, has not been demonstrated in ossifying fibroma. We sought to determine if loss of parafibromin regularly contributes to the development of sporadic, nonsyndromic ossifying fibroma. We examined a series of 9 ossifying fibromas, including ossifying, cemento-ossifying, and juvenile active variants, for parafibromin protein expression by immunohistochemistry and for sequence abnormalities by Sanger sequencing and/or targeted AmpliSeq panel sequencing. Read More

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Comprehensive molecular profiling of pulmonary pleomorphic carcinoma.

NPJ Precis Oncol 2021 Jun 22;5(1):57. Epub 2021 Jun 22.

Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.

Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. We sequenced the DNAs and RNAs of 78 specimens from 52 patients with PPC. Read More

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Frequent POLE-driven hypermutation in ovarian endometrioid cancer revealed by mutational signatures in RNA sequencing.

BMC Med Genomics 2021 Jun 22;14(1):165. Epub 2021 Jun 22.

Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

Background: DNA polymerase epsilon (POLE) is encoded by the POLE gene, and POLE-driven tumors are characterized by high mutational rates. POLE-driven tumors are relatively common in endometrial and colorectal cancer, and their presence is increasingly recognized in ovarian cancer (OC) of endometrioid type. POLE-driven cases possess an abundance of TCT > TAT and TCG > TTG somatic mutations characterized by mutational signature 10 from the Catalog of Somatic Mutations in Cancer (COSMIC). Read More

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