scholarly journals Low-grade Appendiceal Mucinous Neoplasm (Appendiceal Villous Adenoma) with Cystic Fibrosis: A Case Report

2021 ◽  
Vol 20 (1) ◽  
pp. 27-31
Author(s):  
Emrah Doğan ◽  
Hakan Hakan Avcı ◽  
Muge Kuzu Avcı ◽  
Korkut Bozkurt ◽  
Ozge Oral Tapan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Villous Adenoma ◽  
Autosomal Dominant ◽  
Low Grade ◽  
Radiological Findings ◽  
Appendiceal Tumor ◽  
Colon Cancers ◽  
Regulator Protein ◽  
Dominant Disease ◽  
Secretory Glands

Cystic fibrosis (CF) is an autosomal dominant disease characterized by the dysfunction of exocrine secretory glands resulting from a mutation in the transmembrane regulator protein (CFTR) gene. As life expectancy increases in patients with cystic fibrosis secondary to advances in treatment, advanced age malignancies secondary to cystic fibrosis emerge. Especially, the frequency of gastrointestinal system malignancies and colon cancers increases with aging. Appendiceal tumors are a rare entity and constitute less than 1% of gastrointestinal tumors. We presented a villous adenoma encountered in an 18-year-old male patient with CF accompanied by clinical and radiological findings. Our case is the first reported appendiceal tumor that emerged in patients with cystic fibrosis.

scholarly journals A family harboring an MLKL loss of function variant implicates impaired necroptosis in diabetes

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Joanne M. Hildebrand ◽  
Bernice Lo ◽  
Sara Tomei ◽  
Valentina Mattei ◽  
Samuel N. Young ◽  
...  
Keyword(s):  
Potential Role ◽  
Autosomal Dominant ◽  
Inflammatory Diseases ◽  
Diabetic Patients ◽  
Incomplete Penetrance ◽  
Loss Of Function ◽  
Healthy Sibling ◽  
Dominant Disease ◽  
Terminal Effector

AbstractMaturity-onset diabetes of the young, MODY, is an autosomal dominant disease with incomplete penetrance. In a family with multiple generations of diabetes and several early onset diabetic siblings, we found the previously reported P33T PDX1 damaging mutation. Interestingly, this substitution was also present in a healthy sibling. In contrast, a second very rare heterozygous damaging mutation in the necroptosis terminal effector, MLKL, was found exclusively in the diabetic family members. Aberrant cell death by necroptosis is a cause of inflammatory diseases and has been widely implicated in human pathologies, but has not yet been attributed functions in diabetes. Here, we report that the MLKL substitution observed in diabetic patients, G316D, results in diminished phosphorylation by its upstream activator, the RIPK3 kinase, and no capacity to reconstitute necroptosis in two distinct MLKL−/− human cell lines. This MLKL mutation may act as a modifier to the P33T PDX1 mutation, and points to a potential role of impairment of necroptosis in diabetes. Our findings highlight the importance of family studies in unraveling MODY’s incomplete penetrance, and provide further support for the involvement of dysregulated necroptosis in human disease.

scholarly journals A novel TSC1 variant associated with tuberous sclerosis and sacrococcygeal teratoma

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Saba Ahmad ◽  
Luis Manon ◽  
Gifty Bhat ◽  
Jerry Machado ◽  
Alice Zalan ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Cellular Differentiation ◽  
Autosomal Dominant ◽  
De Novo ◽  
Autosomal Dominant Disease ◽  
Sacrococcygeal Teratoma ◽  
Dominant Disease ◽  
The Brain

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disease associated with tumors and malformed tissues in the brain and other vital organs. We report a novel de novo frameshift variant of the TSC1 gene (c.434dup;p. Ser146Valfs*8) in a child with TSC who initially presented with a sacral teratoma. This previously unreported association between TSC and teratoma has broad implications for the pathophysiology of embryonic tumors and mechanisms underlying cellular differentiation.

scholarly journals Dysembryoplastic neuroepithelial tumor and oligodendroglioma: the diagnostic value of magnetic resonance spectroscopy

1998 ◽  
Vol 4 (4) ◽  
pp. E8 ◽  
Author(s):  
Eric W. Sherburn ◽  
Mark M. Bahn ◽  
Murat Gokden ◽  
Daniel L. Silbergeld ◽  
Keith M. Rich
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Treatment Options ◽  
Diagnostic Value ◽  
Low Grade Glioma ◽  
Resonance Spectroscopy ◽  
Dysembryoplastic Neuroepithelial Tumor ◽  
Low Grade ◽  
Radiological Findings ◽  
Similar Treatment

Preoperative differentiation between dysembryoplastic neuroepithelial tumor (DNT) and low-grade glioma is often not possible. Dysembryoplastic neuroepithelial tumor is a recently described entity of uncertain origin; however, the diagnosis has important clinical implications. Clinical and radiological findings of DNT and low-grade glioma, especially oligodendroglioma, may be similar. Treatment options and prognosis differ significantly between these two lesions; consequently, accurate diagnosis is imperative. The authors describe two individuals who presented simultaneously at their institution: one patient with an oligodendroglioma and a second patient with DNT. The natural history, neurodiagnostic, and pathological features of each are reviewed with special emphasis on the potential utility of magnetic resonance spectroscopy in differentiating these lesions.

Impaired social cognition and fine dexterity in patients with Cowden syndrome associated with germline PTEN variants

2021 ◽  
pp. jmedgenet-2021-107954
Author(s):  
Clément Desjardins ◽  
Frédéric Caux ◽  
Bertrand Degos ◽  
Djallel Benzohra ◽  
Astrid De Liège ◽  
...  
Keyword(s):  
Social Cognition ◽  
Neuropsychological Assessment ◽  
Splice Site ◽  
Autosomal Dominant ◽  
Neuropsychological Functioning ◽  
Cowden Syndrome ◽  
Increased Risk ◽  
Cerebral Mri ◽  
Dominant Disease ◽  
Brain Alteration

PurposeCowden syndrome (CS) is an autosomal dominant disease related to germline PTEN variants and is characterised by multiple hamartomas, increased risk of cancers and frequent brain alteration. Since the behaviour of patients with CS sometimes appears to be inappropriate, we analysed their neuropsychological functioning.MethodsThis monocentric study was conducted between July 2018 and February 2020. A standardised neuropsychological assessment, including an evaluation of social cognition, executive functions, language and dexterity, as well as a cerebral MRI were systematically proposed to all patients with CS. Moreover, PTEN variants were identified.ResultsFifteen patients from 13 families were included, with six non-sense (40%), three missense (20%), five frameshift (33.3%) and one splice site (6.6%) variant types. Twelve patients (80%) had altered social cognition: 10 patients had an abnormal modified Faux-Pas score and 5 had Ekman’s facial emotions recognition impairment. Nearly all patients (93%) had impaired dexterity. Cerebral MRI showed various cerebellar anomalies in seven patients (46.7%).ConclusionAltered social cognition and impaired fine dexterity are frequently associated with CS. Further studies are needed to confirm these results and to determine whether dexterity impairment is due to the effect of germline PTEN variants in the cerebellum.

scholarly journals The Formation of the cAMP/Protein Kinase A-dependent Annexin 2–S100A10 Complex with Cystic Fibrosis Conductance Regulator Protein (CFTR) Regulates CFTR Channel Function

2007 ◽  
Vol 18 (9) ◽  
pp. 3388-3397 ◽  
Author(s):  
Lee A. Borthwick ◽  
Jean Mcgaw ◽  
Gregory Conner ◽  
Christopher J. Taylor ◽  
Volker Gerke ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Complex Analysis ◽  
Short Circuit ◽  
Disulfonic Acid ◽  
Intestinal Biopsy ◽  
Regulator Protein ◽  
Annexin 2 ◽  
Kinase A

Cystic fibrosis results from mutations in the cystic fibrosis conductance regulator protein (CFTR), a cAMP/protein kinase A (PKA) and ATP-regulated Cl− channel. CFTR is increasingly recognized as a component of multiprotein complexes and although several inhibitory proteins to CFTR have been identified, protein complexes that stimulate CFTR function remain less well characterized. We report that annexin 2 (anx 2)–S100A10 forms a functional cAMP/PKA/calcineurin (CaN)-dependent complex with CFTR. Cell stimulation with forskolin/3-isobutyl-1-methylxanthine significantly increases the amount of anx 2–S100A10 that reciprocally coimmunoprecipitates with cell surface CFTR and calyculin A. Preinhibition with PKA or CaN inhibitors attenuates the interaction. Furthermore, we find that the acetylated peptide (STVHEILCKLSLEG, Ac1-14), but not the nonacetylated equivalent N1-14, corresponding to the S100A10 binding site on anx 2, disrupts the anx 2–S100A10/CFTR complex. Analysis of 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) and CFTRinh172-sensitive currents, taken as indication of the outwardly rectifying Cl− channels (ORCC) and CFTR-mediated currents, respectively, showed that Ac1-14, but not N1-14, inhibits both the cAMP/PKA-dependent ORCC and CFTR activities. CaN inhibitors (cypermethrin, cyclosporin A) discriminated between ORCC/CFTR by inhibiting the CFTRinh172-, but not the DIDS-sensitive currents, by >70%. Furthermore, peptide Ac1-14 inhibited acetylcholine-induced short-circuit current measured across a sheet of intact intestinal biopsy. Our data suggests that the anx 2–S100A10/CFTR complex is important for CFTR function across epithelia.

scholarly journals Clinical case of myocardial infarction with unspecified familial hypercholesterolemia

2022 ◽  
Vol 17 (4) ◽  
pp. 74-78
Author(s):  
N. G. Lozhkina ◽  
A. N. Spiridonov
Keyword(s):  
Myocardial Infarction ◽  
Familial Hypercholesterolemia ◽  
Clinical Case ◽  
Autosomal Dominant ◽  
Clinical Symptoms ◽  
Cholesterol Metabolism ◽  
Single Gene ◽  
Low Density Lipoproteins ◽  
Dominant Disease ◽  
Appropriate Therapy

Familial hypercholesterolemia is a hereditary autosomal dominant disease characterized by a violation of cholesterol metabolism. This nosology was first described in the late 1930s by the Norwegian clinician Karl Moeller, he proposed the idea that hypercholesterolemia and tendon xanthomas are associated with cardiovascular diseases through the inheritance of a single gene. In 1964, two clinical phenotypes of familial hypercholesterolemia were discovered: heterozygous and homozygous, associated with an unfavorable prognosis. To date, it is known that the long-running process of accumulation of low-density lipoproteins in the intima of blood vessels may not have clinical symptoms for many years due to the developed system of collaterals and the absence of hemodynamically significant stenosis. However, without timely diagnosis and appropriate therapy, this condition inevitably leads to the development of a cardiovascular event. The article presents a clinical case demonstrating the development of myocardial infarction in a patient with a late diagnosis of this disease.

DLX3 Mutation in a New Family and Its Phenotypic Variations

2008 ◽  
Vol 87 (4) ◽  
pp. 354-357 ◽  
Author(s):  
S.-K. Lee ◽  
Z.H. Lee ◽  
S.-J. Lee ◽  
B.-D. Ahn ◽  
Y.-J. Kim ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Autosomal Dominant ◽  
Mutational Analysis ◽  
Enamel Hypoplasia ◽  
Enamel Defects ◽  
Clinical Phenotypes ◽  
New Family ◽  
Dominant Disease ◽  
Curly Hair ◽  
Phenotypic Variations

Tricho-dento-osseous syndrome (TDO) is an autosomal-dominant disease characterized by curly hair at birth, enamel hypoplasia, taurodontism, and a thick cortical bone. A common DLX3 gene mutation (c.571_574delGGGG) has been identified in multiple families with variable clinical phenotypes. Recently, another DLX3 gene mutation (c.561_562delCT) was reported to cause amelogenesis imperfecta with taurodontism (AIHHT). We identified a Korean family with overlapping phenotypes of TDO and AIHHT. We performed mutational analysis to discover its genetic etiology. The identified mutation was c.561_562delCT mutation in the DLX3 gene. The enamel was hypomature and hypoplastic. The characteristic taurodontic features were not identified. Increased bone density or thickness could not be revealed by cephalometric, hand-wrist, and panoramic radiographs. Affected individuals reported that their nails were brittle, and they had curly hair at birth. This study clearly showed that the c.561_562delCT mutation had not only enamel defects, but also other clinical phenotypes resembling those of TDO syndrome.

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