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Autosomal Dominant Non-Syndromic Sensorineural Hearing Loss
Published in John C Watkinson, Raymond W Clarke, Christopher P Aldren, Doris-Eva Bamiou, Raymond W Clarke, Richard M Irving, Haytham Kubba, Shakeel R Saeed, Paediatrics, The Ear, Skull Base, 2018
Polona Le Quesne Stabej, Maria Bitner-Glindzicz
So, although some non-syndromic AD SNHL loci are associated with particular audiometric patterns or clinical presentations, such as mutations in COCH, also giving rise to prominent vestibular symptoms, a sufficiently distinctive, unique audiogram or clinical picture to confidently enable clinical diagnosis is unusual. This has spurred the development of ‘AudioGene’, an online automated tool which automatically analyzes audiometric data to predict the likely underlying genetic causes of hearing loss. It has been shown to have some success in predicting the gene/locus responsible for deafness based on audiogram,4 particularly for KCNQ4 mutations which cause a pattern of mainly high-frequency hearing loss and which has been found to be a relatively common form of dominantly inherited hearing loss.5,6 Audioprofiles for many other loci have now been compiled and are available for use to try to predict the gene or locus involved based purely on audiometric pattern and progression. The currently known AD genes for SNHL are outlined in Table 58.1, together with age of onset and audiometric description.
Waardenburg syndrome: characteristics and long-term outcomes of paediatric cochlear implant recipients
Published in Hearing, Balance and Communication, 2019
Pedro Clarós, Agnieszka Remjasz, Astrid Clarós-Pujol, Carmen Pujol, Andrés Clarós
Referring to the variable phenotypic expressivity of WS, the genetic differentiation also creates significant challenges for both clinical diagnosis and genetic counselling. Many causative genes were identified for WS and are the basis of disorder classification. WS type 1 and WS type 3 are associated with mutations of the PAX3 gene located on chromosome band 2q35. The primary subtype of WS type 2 results from mutations in the MITF (melanogenesis associated transcription factor, otherwise called homolog of mouse microphthalmia) on the SNA12 gene located on chromosome band 3p14. Some mutations at loci 1-p12.3, 8p23 and 8q11 cause different subtypes of WS type 2, while another case suspected to be WS type 2 due to the same symptoms, does not present any mutations in these locations. WS type 4 follows on mutations in the SOX10, EDN3 or EDNRB [4]. Additionally, these genes are not only responsible for the formation of the melanin, but also the development of nerve cells of the large intestine. Mutations in any of these genes result in hearing loss (HL), problems with pigmentation and intestinal issues related to Hirschsprung disease [5,6]. It should also be mentioned that some genes present in WS, are associated with deafness and HL, such as DIAPH1, KCNQ4, GJB3, GJB2, GJB6, MYH14, DFNA5, WFS1, TECTA and COCH [7].
Down-expression of P2RX2, KCNQ5, ERBB3 and SOCS3 through DNA hypermethylation in elderly women with presbycusis
Published in Biomarkers, 2018
Amal Bouzid, Ibtihel Smeti, Leila Dhouib, Magali Roche, Imen Achour, Aida Khalfallah, Abdullah Ahmed Gibriel, Ilhem Charfeddine, Hammadi Ayadi, Joel Lachuer, Abdelmonem Ghorbel, Christine Petit, Saber Masmoudi
Both KCNQ5 and P2RX2 ion channels were previously described in inner ear. KCNQ5, potassium channel voltage gated KQT-like subfamily Q member 5, is highly expressed in the inner ear (Spitzmaul et al. 2013) of mouse models and adult zebrafish (Wu et al. 2014) as well as in guinea pig and rat cochlea (Liang et al. 2006). Voltage-gated potassium channels play key roles in hearing, as evidenced by deafness resulting from disruption of genes encoding, for example, KCNQ1 or KCNQ4 subunits. P2RX2, purinergic receptor P2X ligand gated ion channel 2, mediates variety of cellular responses including excitatory postsynaptic responses in sensory neurons. It acts as a key signaling molecule involved in normal cochlear homeostasis and hearing sensitivity (Thorne et al. 2002). Reduced P2RX2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea resulted in hearing sensitivity impairment (Telang et al. 2010). Haplo-insufficiency in P2RX2 gene causes human autosomal dominant deafness (DFNA41) characterized by onset of progressive high-frequency sensorineural HI usually in the second decade (Yan et al. 2013). In this case, DNA methylation changes and down-expression of the P2RX2 gene may account for function disruption of the inner ear.
Kv7 channel inhibition increases hypoxic pulmonary vasoconstriction in endotoxemic mouse lungs
Published in Experimental Lung Research, 2020
Maurizio Turzo, Fabian A. Spöhr, Lasitschka Felix, Markus A. Weigand, Cornelius J. Busch
Impaired HPV induced by endotoxemia can be augmented with the pharmacologic inhibitors LI or the sulfonamide analogue HMR1556. While KCNQ1, KCNQ4 as well as KCNQ5 gene- and protein expressions were unaltered in endotoxemic mouse lungs, KCNE3 gene and protein expressions were increased. KCNE3 protein was detected in smooth muscle cells of pulmonary arteries, bronchioles and connective tissue.