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Pendred Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
There is tangible evidence that mutations in the FOXI1 gene on chromosome 5q35.1 encoding forkhead box protein I1 and the KCNJ10 gene on chromosome 1q23.2 encoding the ATP-sensitive inward rectifier potassium channel 10 may be implicated in about 2% of non-classic Pendred syndrome (also known as nonsyndromic enlarged vestibular aqueduct [NSEVA]), but not classic Pendred syndrome. Further, biallelic KCNJ10 pathogenic variants are involved in SeSAME syndrome (seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance) and EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) [17,18].
99mTc-Sestamibi SPECT/CT and histopathological features of oncocytic renal neoplasia
Published in Scandinavian Journal of Urology, 2022
Antonios Tzortzakakis, Thomas Papathomas, Ove Gustafsson, Stefan Gabrielson, Kiril Trpkov, Linnea Ekström-Ehn, Alexandros Arvanitis, Maria Holstensson, Mattias Karlsson, Georgia Kokaraki, Rimma Axelsson
Immunohistochemistry plays a major role in renal tumour diagnostics due to its widespread availability; a panel comprising cytokeratin 7 (CK7)/carbonic anhydrase IX (CAIX)/alpha-methyl acyl-CoA racemase (AMACR)/KIT (CD117) may be used for screening [33]. Other emerging markers such as FOXI1, RHCG, and LINC01187 that appear lineage-specific for renal epithelial neoplasms arising from intercalated cells in the distal nephron segment, may also play a role in the future [34]. Nevertheless, immunohistochemistry limitations are well known in routine practice, and slight differences in the immunohistochemical profiles have also been identified among HOCT subtypes (i.e. Birt-Hogg-Dubé syndrome, renal oncocytosis/oncocytomatosis and sporadic tumours) [35]. Other approaches to potentially identify unique oncocytic tumour-specific features include (i) whole scale approach of computer-assisted morphometry [36], (ii) molecular genetic approaches, including gene expression, microRNA, single-nucleotide polymorphism (SNP), array comparative genomic hybridisation (array-CGH) profiling analyses [37,38] as well as the recently proposed oncocytic nine gene classifier by McGillivray et al. [39] and (iii) an in-situ metabolomic approach [40].
Emerging gene therapies for cystic fibrosis
Published in Expert Review of Respiratory Medicine, 2019
Kamran M. Miah, Stephen C. Hyde, Deborah R. Gill
The presence of airway epithelial tissue stem cells has long been debated, although lung progenitor cells have been characterized. The alveolar epithelial progenitor (AEP) lineage in the distal lung [135] is a major contributor to the regeneration of epithelial cells in the parenchyma, specifically alveolar type (AT) −1 and −2 cells. In the airways, many studies indicate that the airway epithelium is maintained by basal cell progenitors [136,137]. This is important, given the potential use of lentiviral vectors as a gene delivery tool ex vivo for long-lived CF correction [138,139], although methods to expand patient-specific basal cells to a therapeutically relevant density require further refinement to retain basal cells with regenerative potential [139]. Two independent studies identified pulmonary ionocytes as an infrequent population (~1%) of airway epithelial cells derived from basal cells, which are positive for Foxi1 and V-ATPase, and contribute >50% of total CFTR transcripts compared with 1.5% from ciliated cells (the prototypical target cell for CF gene therapy) [140,141]. The relative contribution of these cells to CF lung disease can be inferred from Foxi1 knockout mouse primary epithelia cultures that correlated with a significant loss in CFTR expression and a resemblance to mouse CF pathophysiology (increased mucus viscosity and increased frequency in cilia beating) [140]. The identification of ionocytes as a major contributor to total CFTR expression begs the question: to what extent do ionocytes function in human airway physiology and in CF lung disease given the exceedingly low ionocyte population density? Targeted replacement or correction of mutated CFTR in pulmonary ionocytes in vivo may not confer elevated CFTR expression and activity, seeing as the endogenous FOXI1 transcription factor seems to regulate endogenous CFTR expression in this cell lineage by an as yet uncharacterized mechanism.