Congenital hereditary endothelial dystrophy with progressive sensorineural deafness (Harboyan syndrome)

Désir, Julie; Abramowicz, Marc

doi:10.1186/1750-1172-3-28

Cited by 55 publications

(58 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In an earlier study using a mouse inner ear microarray, Slc4a11 message was detected in the lateral wall of the cochlea (24). This finding was interpreted as having localized the cotransporter to the stria vascularis (14). However, our results demonstrate that NaBC1 is indeed highly expressed in the lateral wall and localized in spiral ligament fibrocytes rather than the stria vascularis.…”

Section: Discussioncontrasting

confidence: 55%

“…Our results demonstrate that Slc4a11 Ϫ/Ϫ mice are an important new model system for addressing the underlying pathophysiology of the sensory abnormalities in patients with NaBC1 mutations (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Prior to the current study, there was no information regarding the expression of NaBC1 protein in the inner ear.…”

Section: Discussionmentioning

confidence: 87%

“…Therefore, the corneal phenotype in Slc4A11 Ϫ/Ϫ mice differ significantly from the severe corneal phenotype described in patients with mutations in the SLC4A11 gene (5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Examples Of Typical Vsep Waveforms In Slc4a11mentioning

confidence: 99%

“…Mutations in the SLC4A11 gene are responsible for corneal hereditary dystrophy type 2 (CHED2) 4 and Harboyan syndrome (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In addition to corneal dystrophy, patients with Harboyan syndrome have perceptive hearing loss and nystagmus (7,14).…”

mentioning

confidence: 99%

“…In addition to corneal dystrophy, patients with Harboyan syndrome have perceptive hearing loss and nystagmus (7,14). Whether all patients with CHED2 have undiagnosed hearing abnormalities is currently unknown.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Slc4a11 Gene Disruption in Mice

López

Rosenblatt

Kim

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

NaBC1 (the SLC4A11 gene) belongs to the SLC4 family of sodium-coupled bicarbonate (carbonate) transporter proteins and functions as an electrogenic sodium borate cotransporter. Mutations in SLC4A11 cause either corneal abnormalities (corneal hereditary dystrophy type 2) or a combined auditory and visual impairment (Harboyan syndrome). The role of NaBC1 in sensory systems is poorly understood, given the difficulty of studying patients with NaBC1 mutations. We report our findings in Slc4a11 ؊/؊ mice generated to investigate the role of NaBC1 in sensorineural systems. In wild-type mice, specific NaBC1 immunoreactivity was detected in fibrocytes of the spiral ligament, from the basal to the apical portion of the cochlea. NaBC1 immunoreactivity was present in the vestibular labyrinth, in stromal cells underneath the non-immunoreactive sensory epithelia of the macula utricle, sacule, and crista ampullaris, and the membranous vestibular labyrinth was collapsed. Both auditory brain response and vestibular evoked potential waveforms were significantly abnormal in Slc4a11 ؊/؊ mice. In the cornea, NaBC1 was highly expressed in the endothelial cell layer with less staining in epithelial cells. However, unlike humans, the corneal phenotype was mild with a normal slit lamp evaluation. Corneal endothelial cells were morphologically normal; however, both the absolute height of the corneal basal epithelial cells and the relative basal epithelial cell/total corneal thickness were significantly increased in Slc4a11 ؊/؊ mice. Our results demonstrate for the first time the importance of NaBC1 in the audio-vestibular system and provide support for the hypothesis that SLC4A11 should be considered a potential candidate gene in patients with isolated sensorineural vestibular hearing abnormalities.The SLC4 transporter family consists of proteins that mediate bicarbonate (carbonate) transport and include Cl-HCO 3 exchangers, Na/HCO 3 cotransporters, and sodium-driven Cl-HCO 3 exchangers (1). A single member of the family encoded by the SLC4A11 gene does not transport bicarbonate (carbonate) (2, 3). On the basis of sequence homology with other members of the SLC4 family, the protein encoded by SLC4A11 was initially called BTR1 (bicarbonate transporter 1) (2). Subsequently, motivated by its homology with the borate transporter BOR1 in Arabidopsis (4), experiments by Park et al. (3) reported that the transporter functioned in the presence of borate as an electrogenic sodium-borate cotransporter and was renamed NaBC1.Mutations in the SLC4A11 gene are responsible for corneal hereditary dystrophy type 2 (CHED2) 4 and Harboyan syndrome (5-14). In addition to corneal dystrophy, patients with Harboyan syndrome have perceptive hearing loss and nystagmus (7,14). Whether all patients with CHED2 have undiagnosed hearing abnormalities is currently unknown. Heterozygous single nucleotide polymorphisms for SLC4A11 have also been identified in Chinese and Indian patients with Fuchs dystrophy, the most common dystrophic cause of endothelial failure in the...

show abstract

Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 87%

Section: Examples Of Typical Vsep Waveforms In Slc4a11mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Slc4a11 Gene Disruption in Mice

López

Rosenblatt

Kim

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Classification of Posterior Polymorphous Corneal Dystrophy as a Corneal Ectatic Disorder Following Confirmation of Associated Significant Corneal Steepening

et al. 2013

View full text Add to dashboard Cite

Oligomerization of SLC4A11 protein and the severity of FECD and CHED2 corneal dystrophies caused bySLC4A11mutations

et al. 2011

View full text Add to dashboard Cite

Mutations in the SLC4A11 gene, which encodes a plasma membrane borate transporter, cause recessive congenital hereditary endothelial corneal dystrophy type 2 (CHED2), corneal dystrophy and perceptive deafness (Harboyan syndrome), and dominant late-onset Fuchs endothelial corneal dystrophy (FECD). We analyzed missense SLC4A11 mutations identified in FECD and CHED2 patients and expressed in transfected HEK 293 cells. Chemical cross-linking and migration in nondenaturing gels showed that SLC4A11 exists as a dimer. Furthermore, co-immunoprecipitation of epitope-tagged proteins revealed heteromeric interactions between wild-type (WT) and mutant SLC4A11 proteins. When expressed alone, FECD- and CHED2-causing mutant SLC4A11 proteins are primarily retained intracellularly. Co-expression with WT SLC4A11 partially rescued the cell surface trafficking of CHED2 mutants, but not FECD mutants. CHED2 alleles of SLC4A11 did not affect cell surface processing of WT SLC4A11. In contrast, FECD mutants reduced WT cell surface processing efficiency, consistent with dominant inheritance of FECD. The reduction in movement of WT protein to the cell surface caused by FECD SLC4A11 helps to explain the dominant inheritance of this disorder. Similarly, the failure of CHED2 mutant SLC4A11 to affect the processing of WT protein, explains the lack of symptoms found in CHED2 carriers and the recessive inheritance of the disorder.

show abstract

Congenital hereditary endothelial dystrophy with progressive sensorineural deafness (Harboyan syndrome)

Cited by 55 publications

References 42 publications

Slc4a11 Gene Disruption in Mice

Slc4a11 Gene Disruption in Mice

Classification of Posterior Polymorphous Corneal Dystrophy as a Corneal Ectatic Disorder Following Confirmation of Associated Significant Corneal Steepening

Oligomerization of SLC4A11 protein and the severity of FECD and CHED2 corneal dystrophies caused bySLC4A11mutations

Contact Info

Product

Resources

About