scholarly journals Molecular and Clinical Insights in Malignant Brenner Tumor of the Testis With Liver Metastases:A Case Report

2021 ◽  
Vol 11 ◽  
Author(s):  
Pietro Parcesepe ◽  
Luigi Coppola ◽  
Andrea Remo ◽  
Mario Rosario D’Andrea ◽  
Giulia Coppola ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Ovarian Neoplasms ◽  
Mutational Analysis ◽  
Clinical Course ◽  
Molecular Testing ◽  
Missense Mutations ◽  
First Case ◽  
Brenner Tumor ◽  
Personalized Approach ◽  
Multiple Liver Metastases

Malignant Brenner Tumor (mBT) is extremely rare. Although BT are almost exclusive ovarian neoplasms, they may constitute a highly unusual tumor of the testis; in fact, only seven fully documented cases have been reported to date. Because of their rarity, the pathogenesis of these tumors has not been clarified and there is no standard therapeutic approach. We report the first case of epididymal mBT with synchronous, multiple, liver metastases and a very dramatic clinical course. Both primary tumor and metastasis were subjected to mutational analysis of 20 cancer associated genes. Primary tumor showed FGFR3 Tyr375Cys and PIK3CA His1047Arg missense mutations. Both mutations are reported as pathogenic in ClinVar database. The same FGFR3 mutation was present in liver metastasis. Based on these results we believe that the FGFR pathway could be an ideal candidate for personalized treatment, offering hope to a subset of patients with mBT. Personalized approach, including mutational analysis and molecular testing should be required in patients with rare tumors in order to clarify diagnosis and improve therapeutic strategies.

scholarly journals Clinical Manifestations, Mutational Analysis, and Immunological Phenotype in Patients With RAG1/2 Mutations: First Cases Series From Mexico and Description of Two Novel Mutations.

2021 ◽  
Author(s):  
Mario Ernesto Cruz-Munoz ◽  
Saul Oswaldo Lugo-Reyes ◽  
Nina Pastor ◽  
Edith González-Serrano ◽  
Marco Yamazaki-Nakashimada ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Severe Combined Immunodeficiency ◽  
Clinical Manifestations ◽  
Case Series ◽  
Missense Mutations ◽  
Antigen Receptors ◽  
Novel Mutations ◽  
Nonsense Mutations ◽  
First Case ◽  
Immunological Phenotype

Abstract Mutations in Recombinase Activating Genes 1 and 2 (RAG1/2) results in human severe combined immunodeficiency (SCID). The products of these genes, are essential for V(D)J rearrangement of the antigen receptors during lymphocyte development. Nonsense mutations in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with missense mutations may develop leaky SCID or Omenn syndrome (OS). A group of non-previously recognized clinical phenotypes associated with granulomata and/or autoimmunity have been described as a consequence of hypomorphic mutations. Here we present six patients from unrelated families with missense variants in RAG1 or RAG2. Phenotypes observed in these patients ranged from OS to severe mycobacterial infections and granulomatous disease. Moreover, we report the first evidence of two previously unidentified variants as causative of pathological manifestations associated to immunodeficiency. This study represents the first case series of RAG1 or RAG2 deficient patients from Mexico and Latin America.

scholarly journals Mutational Analysis of a Histone Deacetylase in Drosophila melanogaster: Missense Mutations Suppress Gene Silencing Associated With Position Effect Variegation

Genetics ◽  
2000 ◽  
Vol 154 (2) ◽  
pp. 657-668 ◽  
Author(s):  
Randy Mottus ◽  
Richard E Sobel ◽  
Thomas A Grigliatti
Keyword(s):  
Drosophila Melanogaster ◽  
Histone Deacetylase ◽  
Transcriptional Activity ◽  
Mutational Analysis ◽  
Position Effect ◽  
Transcriptional Regulator ◽  
Position Effect Variegation ◽  
Missense Mutations ◽  
Effect Variegation ◽  
New Mutations

Abstract For many years it has been noted that there is a correlation between acetylation of histones and an increase in transcriptional activity. One prediction, based on this correlation, is that hypomorphic or null mutations in histone deacetylase genes should lead to increased levels of histone acetylation and result in increased levels of transcription. It was therefore surprising when it was reported, in both yeast and fruit flies, that mutations that reduced or eliminated a histone deacetylase resulted in transcriptional silencing of genes subject to telomeric and heterochromatic position effect variegation (PEV). Here we report the first mutational analysis of a histone deacetylase in a multicellular eukaryote by examining six new mutations in HDAC1 of Drosophila melanogaster. We observed a suite of phenotypes accompanying the mutations consistent with the notion that HDAC1 acts as a global transcriptional regulator. However, in contrast to recent findings, here we report that specific missense mutations in the structural gene of HDAC1 suppress the silencing of genes subject to PEV. We propose that the missense mutations reported here are acting as antimorphic mutations that “poison” the deacetylase complex and propose a model that accounts for the various phenotypes associated with lesions in the deacetylase locus.

scholarly journals Mutation screening of the thyroid peroxidase gene in a cohort of 55 Portuguese patients with congenital hypothyroidism

2005 ◽  
Vol 152 (2) ◽  
pp. 193-198 ◽  
Author(s):  
Carina Rodrigues ◽  
Paula Jorge ◽  
José Pires Soares ◽  
Isaura Santos ◽  
Regina Salomão ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Mutation Screening ◽  
Gene Mutations ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Molecular Testing ◽  
Missense Mutations ◽  
Human Thyroid Peroxidase ◽  
Iodide Organification Defect ◽  
Organification Defect

Objective: Defects in the human thyroid peroxidase (TPO) gene are reported to be one of the causes of congenital hypothyroidism (CH) due to a total iodide organification defect. The aim of the present study was to determine the nature and frequency of TPO gene mutations in patients with CH, characterised by elevated TSH levels and orthotopic thyroid gland, identified in the Portuguese National Neonatal Screening Programme. Subjects and methods: The sample comprised 55 patients, from 53 unrelated families, with follow-up in the endocrinology clinics of the treatment centres of Porto and Lisbon. Mutation screening in the TPO gene (exons 1–17) was performed by single-strand conformational analysis followed by sequencing of fragments with abnormal migration patterns. Results: Eight different mutations were detected in 13 patients (seven homozygotes and six compound heterozygotes). Novel mutations included three missense mutations, namely 391T > C (S131P), 1274A > G (N425S) and 2512T > A (C838S), as well as the predictable splice mutation 2748G > A (Q916Q/spl?). The undocumented polymorphism 180-47A > C was also detected. Conclusion: The results are in accordance with previous observations confirming the genetic heterogeneity of TPO defects. The proportion of patients in which the aetiology was determined justifies the implementation of this molecular testing in our CH patients with dyshormonogenesis.

scholarly journals Leptospirosis patient with AIDS the first case reported

1994 ◽  
Vol 27 (1) ◽  
pp. 39-42 ◽  
Author(s):  
Elizabeth de Souza Neves ◽  
Martha Maria Pereira ◽  
Maria Clara Gutierrez Galhardo ◽  
Adriana Caroli ◽  
Jarbas Andrade ◽  
...  
Keyword(s):  
Clinical Course ◽  
Blood Cultures ◽  
Agglutination Test ◽  
Leptospira Interrogans ◽  
First Case ◽  
Positive Urine ◽  
Maximum Titer ◽  
Acquired Immunodeficiency ◽  
Low Levels ◽  
Immunodeficiency Syndrome

A case of renal icterohaemorrhagic leptospirosis involving a patient with acquired immunodeficiency syndrome (AIDS) is reported. Despite the low levels of CD4+ Tlymphocytes, the clinical course of leptospirosis was similar to that observed in non-immunodepressed patients, and no worsening of AIDS occurred due to the infebtion by the spirochete. Serologic conversion was observed in the microscopic agglutination test, with maximum titer of1:3,200. The patient had positive urine cultures for Leptospira interrogans for two months, whereas blood cultures were negative.

scholarly journals CBFA2T3-GLIS2 Fusion Gene Cause Dismal Clinical Course in Acute Megakaryocytic Leukemia of Down Syndrome

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5184-5184
Author(s):  
Nao Takasugi ◽  
Kenichi Amano ◽  
Yasuo Kubota ◽  
Shota Kato ◽  
Yuichi Mitani ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mutational Analysis ◽  
Clinical Course ◽  
Fusion Gene ◽  
Snp Array ◽  
Genomic Analysis ◽  
Array Analysis ◽  
Snp Array Analysis ◽  
Acute Megakaryocytic Leukemia ◽  
Gata1 Mutation

[Introduction] Acute megakaryocytic leukemia of Down syndrome (DS-AMKL) is characterized by excellent outcome with chemotherapy in contrast to non-Down syndrome-related AMKL (non-DS-AMKL). DS-AMKL and non-DS-AMKL have distinct genetic features which may underlie their different clinical characteristics. DS-AMKL is initiated by a GATA1 mutation in the transient abnormal myelopoiesis (TAM) phase and developed with further mutations of other regulators, while non-DS-AMKL is a heterogeneous group which occasionally carry chimeric oncogenes. CBFA2T3-GLIS2 fusion gene is identified in about 30% of children with non-DS-AMKL, and reported as a strong poor prognostic factor in pediatric AMKL. However, CBFA2T3-GLIS2 has never been reported in DS-AMKL and adult AMKL patients. We performed genomic analysis of DS-AMKL including atypical case with difficult clinical course. This is the first report of DS-AMKL harboring the CBFA2T3-GLIS2 fusion gene. [Case] The patient is a 1-year-old female of DS-AMKL with no prior episode of TAM. G-banding analysis revealed the karyotype both of the leukemic cells and normal tissue sample; 47, XX, +21. Chimeric genes of AML1-MTG8, CBFB-MYH, DEK-CAN, MLL-LTG4, MLL-LTG9, MLL-ENL and abnormalities of KIT and FLT3 were not detected. The chemotherapy according to the Japanese Pediatric Leukemia / Lymphoma Study Group AML-D05 protocol, gemtuzumab ozogamicin, IDA-FLAG regimen (idarubicin, fludarabine, cytarabine, filgrastim) and clofarabine-based regimen were tried, but all of them failed to achieve complete remission (CR). She underwent umbilical cord blood transplantation and relapsed on day 35 after transplantation. Once she showed a response to azacitidine, but finally she died on day 293 after transplantation. [Materials and Methods] We performed whole transcriptome sequencing (RNAseq), SNP array analysis, mutational analysis of GATA1 in 6 DS-AMKL samples, which included this refractory sample and five DS-AMKL samples with GATA1 mutations. To analyze gene expression profiling, we applied the hierarchical clustering method and principal component analysis. [Results] RNA sequencing analysis identified a fusion gene involving exon 10 of CBFA2T3 and exon 2 of GLIS2 gene in this refractory sample. This fusion gene was a result of a cryptic inversion on chromosome 16 and the in-frame fusion of both genes. The fusion transcript was validated by reverse transcription-polymerase chain reaction (RT-PCR) followed by Sanger sequencing. Though SNP array analysis confirmed 21 trisomy, it did not identify other copy number aberrations. PCR analysis did not detect GATA1 mutation in this refractory sample, which can be identified in other DS-AMKL samples. Expression analysis elucidated DS-AMKL with CBFA2T3-GLIS2 fusion had distinct expression profile from DS-AMKL with GATA1 mutations. [Discussion] CBFA2T3-GLIS2 fusion is the most common chimeric oncogene identified in non-DS-AMKL children, but has never been detected in DS-AMKL patients. Patients with non-DS-AMKL, especially holding CBFA2T3-GLIS2 fusion gene, have poorer outcomes than DS-AMKL. DS-AMKL patients generally have GATA1 mutations, show high sensitivity to chemotherapy, and can be treated with less intensive chemotherapy. However, our case had no GATA1 mutation and could not achieve CR despite intensive chemotherapy and transplantation. Thus, it is suggested this fusion gene caused the resistance to chemotherapies including hematopoietic stem cell transplantation in our case. Therefore, our case suggests patients with DS-AMKL should be surveyed genomic investigations including RNAseq and mutational analysis of GATA1 to identify their molecular biological subtypes before treatments are initiated. In case that fusion genes are detected in DS-AMKL patients, they must undergo highly intense chemotherapies, looking ahead to transplantation from the beginning of the treatment. Moreover, in case of harboring CBFA2T3-GLIS2 fusion gene, some potential therapies have been proposed, so that efficacy of such new therapies should be validated in a cell line-derived xenograft or patient-derived xenograft model. [Conclusion] DS-AMKL is generally known to show superior outcome, but DS-AMKL without GATA1 mutation and with CBFA2T3-GLIS2 fusion gene shows resistance to chemotherapies. For DS-AMKL patients, it is desirable to perform genomic analysis including RNAseq before chemotherapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Coexistence of Emphysematous Pyelonephritis and Cystitis in a Patient with COVID-19 Complicated with Spontaneous Pneumomediastinum

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Ibrahim Boukhannous ◽  
Anouar El Moudane ◽  
Mehdi Chennoufi ◽  
Mohamed Mokhtari ◽  
Abdelghani Ouraghi ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Clinical Course ◽  
Emphysematous Pyelonephritis ◽  
Perinephric Abscess ◽  
Emphysematous Cystitis ◽  
Spontaneous Pneumomediastinum ◽  
First Case ◽  
Intravenous Antibiotics ◽  
Uremic Syndrome

We report the first case of a 52-year-old nondiabetic male admitted for management of uremic syndrome associated with emphysematous pyelonephritis (EPN), renal and perinephric abscess, and emphysematous cystitis (EC) on a single functional kidney with a large abundance of spontaneous pneumomediastinum (SP) complicating a SARS-CoV-2 pneumonia. The patient has benefited from several dialysis sessions, intravenous antibiotics, and percutaneous drainage. His clinical course was complicated by acute respiratory distress syndrome, and unfortunately, he died nine days following admission.

scholarly journals Mycetoma in Timor-Leste and first report of nocardiosis

2018 ◽  
Vol 10 (3) ◽  
Author(s):  
Nicola Townell ◽  
Thomas Locke ◽  
Margaret Gibbons ◽  
Dan Murphy ◽  
Joshua Francis ◽  
...  
Keyword(s):  
Causative Organism ◽  
Molecular Testing ◽  
High Morbidity ◽  
Middle Income ◽  
Diagnosis And Management ◽  
Middle Income Countries ◽  
First Case ◽  
Soft Tissue Involvement ◽  
Timor Leste ◽  
Resource Issue

Mycetoma is a neglected tropical disease with an unknown global burden. Although considered endemic to South-east Asia, it has not previously been reported from Timor-Lest. We describe two cases in Timor-Leste, highlighting the challenges surrounding microbiological diagnosis and management shared by many low to middle-income countries. As characteristically described, both patients lived rurally and presented late with marked soft tissue involvement and multiple draining sinuses following a prolonged period of high morbidity. Nocardia brasiliensis, a beadedbranched, modified acid-fast, gram-positive bacilli, was isolated and confirmed by molecular testing in the first case. The causative organism in the second case could not be confirmed due to limited microbiological capabilities. Due to limited local laboratory capabilities, Nocardia spp. infection cannot be routinely confirmed in Timor- Leste. However, the microbiology laboratory is essential for the successful diagnosis and management of Mycetoma. In both cases, medical therapy alone resulted in cure and favorable outcomes, although supply of antibiotic remains an ongoing resource issue.

scholarly journals A rare presentation of benign Brenner tumor of ovary: a case report

2018 ◽  
Vol 7 (7) ◽  
pp. 2971
Author(s):  
Sumathi Periasamy ◽  
Subha Sivagami Sengodan ◽  
Devipriya . ◽  
Anbarasi Pandian
Keyword(s):  
Abdominal Pain ◽  
Ovarian Tumor ◽  
Ovarian Neoplasms ◽  
Pelvic Mass ◽  
Ovarian Tumors ◽  
Pathological Examination ◽  
Rare Presentation ◽  
Brenner Tumor ◽  
Benign Nature ◽  
Brenner Tumors

Brenner tumors are rare ovarian tumors accounting for 2-3% of all ovarian neoplasms and about 2% of these tumors are borderline (proliferating) or malignant. These tumors are commonly seen in 4th-8th decades of life with a peak in late 40s and early 50s. Benign Brenner tumors are usually small, <2cm in diameter and often detected incidentally during surgery or on pathological examination. Authors report a case of a large, calcified benign Brenner tumor in a 55-year-old postmenopausal woman who presented with complaint of abdominal pain and mass in abdomen. Imaging revealed large complex solid cystic pelvic mass -peritoneal fibrosarcoma. She underwent laparotomy which revealed huge Brenner tumor weighing 9kg arising from left uterine cornual end extending up to epigastric region. Myomectomy and hysterectomy with bilateral salphingo oophorectomy, omentectomy done and the specimen was sent for histopathological and immunohistochemistry study which revealed benign Brenner tumor. Brenner tumors are rare ovarian neoplasms accounting for 2-3% of all ovarian tumors. Benign Brenner tumors are usually small and solid whereas borderline and malignant Brenner tumors are usually larger and cystic with solid areas. But it is possible to have a completely benign large Brenner tumor. Therefore, benign nature of the lesion should not be excluded even when the ovarian tumor is very large.

scholarly journals Primary Adenosquamous Cell Carcinoma of the Ileum in a Dog

2020 ◽  
Vol 7 (4) ◽  
pp. 155
Author(s):  
Masashi Yuki ◽  
Roka Shimada ◽  
Tetsuo Omachi
Keyword(s):  
Small Intestine ◽  
Case Report ◽  
Cell Carcinoma ◽  
Surgical Resection ◽  
Clinical Course ◽  
Mass Lesion ◽  
Abdominal Radiography ◽  
First Case ◽  
History Of

A 9-year-old male, castrated Chihuahua was examined because of a 7-day history of intermittent vomiting. A mass in the small intestine was identified on abdominal radiography and ultrasonography. Laparotomy revealed a mass lesion originating in the ileum, and surgical resection was performed. The mass was histologically diagnosed as adenosquamous cell carcinoma. Chemotherapy with carboplatin was initiated, but the dog was suspected to have experienced recurrence 13 months after surgery and died 3 months later. To our knowledge, this is the first case report to describe the clinical course of adenosquamous cell carcinoma in the small intestine of a dog.

Sign in / Sign up

Export Citation Format

Share Document