SNOMEDCT: 723828008; ORPHA: 139455; DO: 0050662;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 11q12.3 | Bestrophinopathy, autosomal recessive | 611809 | 3 | BEST1 | 607854 |
A number sign (#) is used with this entry because autosomal recessive bestrophinopathy (ARB) is caused by homozygous or compound heterozygous mutation in the BEST1 gene (607854) on chromosome 11q12.
Burgess et al. (2008) described a distinct retinal disorder they designated autosomal recessive bestrophinopathy (ARB). Characteristics of the disorder included central visual loss, a characteristic retinopathy, an absent electrooculogram (EOG) light rise, and a reduced electroretinogram (ERG). None of the patients showed the vitelliform lesions characteristic of Best disease (153700), but showed a diffuse irregularity of the reflex from the retinal pigment epithelium (RPE), including dispersed punctate flecks. All patients showed an accumulation of fluid within and/or beneath the neurosensory retina in the macula region. All patients were hyperopic, and 3 from 2 families also had angle-closure glaucoma. The severe reduction in the EOG light rise seen in all patients was similar to that seen both in Best disease and ADVIRC (193220).
Lee et al. (2015) described a brother and sister, aged 66 and 52 years, respectively, with molecularly confirmed ARB. Both presented with reduced visual acuity and bilateral symmetrical subretinal deposits of hyperautofluorescent materials in the posterior pole. Spectral-domain optical coherence tomography showed macular thinning with submacular fluid. The sister had a concomitant macular edema associated with branched retinal vein occlusion in the left eye, which responded well to intravitreal bevacizumab injections.
Burgess et al. (2008) sequenced the BEST1 gene (607854) in 5 families and identified DNA variants in each of 10 alleles (see, e.g., 607854.0015). No clinical or electrophysiologic abnormalities were found in heterozygotes. Two missense isoforms severely reduced chloride channel activity. However, unlike 2 other alleles previously associated with Best disease, cotransfection with wildtype bestrophin-1 did not impair the formation of active wildtype bestrophin-1 channels, consistent with the recessive nature of the condition. Thus, Burgess et al. (2008) proposed that ARB is a null phenotype of bestrophin-1 in humans.
Burgess, R., Millar, I. D., Leroy, B. P., Urquhart, J. E., Fearon, I. M., De Baere, E., Brown, P. D., Robson, A. G., Wright, G. A., Kestelyn, P., Holder, G. E., Webster, A. R., Manson, F. D. C., Black, G. C. M. Biallelic mutation of BEST1 causes a distinct retinopathy in humans. Am. J. Hum. Genet. 82: 19-31, 2008. [PubMed: 18179881] [Full Text: https://doi.org/10.1016/j.ajhg.2007.08.004]
Lee, C. S., Jun, I., Choi, S., Lee, J. H., Lee, M. G., Lee, S. C., Kim, E. K. A novel BEST1 mutation in autosomal recessive bestrophinopathy. Invest. Ophthal. Vis. Sci. 56: 8141-8150, 2015. [PubMed: 26720466] [Full Text: https://doi.org/10.1167/iovs.15-18168]