Hearing disability in patients with Fuchs&amp;rsquo; endothelial corneal dystrophy: unrecognized co-pathology?

Stehouwer, Marilette; Bijlsma, Ward R; Lelij, Allegonda Van der

doi:10.2147/opth.s23091

Cited by 14 publications

(16 citation statements)

References 22 publications

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“…Hearing defects found in individuals with FECD (13) and Harboyan syndrome (6) are mirrored in slc4a11 −/− mice (12,14). These mice manifest normal levels of K + in the inner ear's endolymph and evidence of extracellular oedema in the fibrocytes underlying the stria vascularis (12).…”

Section: Discussionmentioning

confidence: 99%

Transmembrane water-flux through SLC4A11: a route defective in genetic corneal diseases

Vilas

Loganathan

et al. 2013

Human Molecular Genetics

139

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Three genetic corneal dystrophies [congenital hereditary endothelial dystrophy type 2 (CHED2), Harboyan syndrome and Fuchs endothelial corneal dystrophy] arise from mutations of the SLC4a11 gene, which cause blindness from fluid accumulation in the corneal stroma. Selective transmembrane water conductance controls cell size, renal fluid reabsorption and cell division. All known water-channelling proteins belong to the major intrinsic protein family, exemplified by aquaporins (AQPs). Here we identified SLC4A11, a member of the solute carrier family 4 of bicarbonate transporters, as an unexpected addition to known transmembrane water movement facilitators. The rate of osmotic-gradient driven cell-swelling was monitored in Xenopus laevis oocytes and HEK293 cells, expressing human AQP1, NIP5;1 (a water channel protein from plant), hCNT3 (a human nucleoside transporter) and human SLC4A11. hCNT3-expressing cells swelled no faster than control cells, whereas SLC4A11-mediated water permeation at a rate about half that of some AQP proteins. SLC4A11-mediated water movement was: (i) similar to some AQPs in rate; (ii) uncoupled from solute-flux; (iii) inhibited by stilbene disulfonates (classical SLC4 inhibitors); (iv) inactivated in one CHED2 mutant (R125H). Localization of AQP1 and SLC4A11 in human and murine corneal (apical and basolateral, respectively) suggests a cooperative role in mediating trans-endothelial water reabsorption. Slc4a11−/− mice manifest corneal oedema and distorted endothelial cells, consistent with loss of a water-flux. Observed water-flux through SLC4A11 extends the repertoire of known water movement pathways and call for a re-examination of explanations for water movement in human tissues.

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Section: Discussionmentioning

confidence: 99%

Transmembrane water-flux through SLC4A11: a route defective in genetic corneal diseases

Vilas

Loganathan

et al. 2013

Human Molecular Genetics

139

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“…FCD was a genetic disorder of the corneal endothelium and was the most common cause of corneal transplantation. Recently, Stehouwer et al reported that rate of hearing disability in FCD group was higher than control group [16]. It suggested an association between FCD and hearing loss.…”

Section: Discussionmentioning

confidence: 99%

Mutations in LOXHD1 Gene Cause Various Types and Severities of Hearing Loss

Mori

Moteki

Kobayashi

et al. 2015

Ann Otol Rhinol Laryngol

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Objective We present two families that were identified with novel mutations in LOXHD1, as a cause of non-progressive hearing loss. Methods One thousand three hundred fourteen (1,314) Japanese subjects with sensorineural hearing loss from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known non-syndromic hearing loss genes were performed to identify the genetic cause of hearing loss. Results Two patients in one family affected with homozygous mutation; c.879+1G>A in LOXHD1, showed profound congenital hearing loss, whereas two patients in the other family with compound heterozygous mutations; c.5869G>T (p.E1957X) and c.4480C>T (p.R1494X) showed moderate to severe hearing loss. Conclusion Mutations in LOXHD1 are extremely rare, and these cases are the first identified in a Japanese population. The genotype-phenotype correlation in LOXHD1 is still unclear. The differences of phenotypes in each patient might be the result of the nature of the mutations, or the location at the gene, or be influenced by genetic modifier.

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“…27 Genetic heterogeneity may exist for CHED2 as some families have no SLC4A11 mutation detected, 12,13,22,25,28 however, only one CHED2 locus has been mapped. 3,4,29 Recently in a study of a non-consanguineous CHED2 Thai family all affected individuals were found to be compound heterozygotes for a novel missense mutation (K260E) and a 68kb deletion which encompasses the SLC4A11 gene; 30 this type of mutation may be the cause of disease in families in which an SLC4A11 gene mutation has not been identified to date.…”

Section: Discussionmentioning

confidence: 99%