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Biallelic mutation of BEST1 causes a distinct retinopathy in humans

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Abstract
We describe a distinct retinal disorder, autosomal-recessive bestrophinopathy (ARB), that is consequent upon biallelic mutation in BEST1 and is associated with central visual loss, a characteristic retinopathy, an absent electro-oculogram light rise, and a reduced electroretinogram. Heterozygous mutations in BEST1 have previously been found to cause the two dominantly inherited disorders, Best macular dystrophy and autosomal-dominant vitreoretinochoroidopathy. The transmembrane protein bestrophin-1, encoded by BEST1, is located at the basolateral membrane of the retinal pigment epithelium in which it probably functions as a Cl- channel. We sequenced BEST1 in five families, identifying DNA variants in each of ten alleles. These encoded six different missense variants and one nonsense variant. The alleles segregated appropriately for a recessive disorder in each family. No clinical or electrophysiological abnormalities were identified in any heterozygotes. We conducted whole-cell patch-clamping of HEK293 cells transfected with bestrophin-1 to measure the Cl- current. Two ARB missense isoforms severely reduced channel activity. However, unlike two other alleles previously associated with Best disease, cotransfection with wild-type bestrophin-1 did not impair the formation of active wild-type bestrophin-1 channels, consistent with the recessive nature of the condition. We propose that ARB is the null phenotype of bestrophin-1 in humans.

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MLA
Burgess, R, ID Millar, Bart Leroy, et al. “Biallelic Mutation of BEST1 Causes a Distinct Retinopathy in Humans.” AMERICAN JOURNAL OF HUMAN GENETICS 82.1 (2008): 19–31. Print.
APA
Burgess, R., Millar, I., Leroy, B., Urquhart, J., Fearon, I., De Baere, E., Brown, P., et al. (2008). Biallelic mutation of BEST1 causes a distinct retinopathy in humans. AMERICAN JOURNAL OF HUMAN GENETICS, 82(1), 19–31.
Chicago author-date
Burgess, R, ID Millar, Bart Leroy, JE Urquhart, IM Fearon, Elfride De Baere, PD Brown, et al. 2008. “Biallelic Mutation of BEST1 Causes a Distinct Retinopathy in Humans.” American Journal of Human Genetics 82 (1): 19–31.
Chicago author-date (all authors)
Burgess, R, ID Millar, Bart Leroy, JE Urquhart, IM Fearon, Elfride De Baere, PD Brown, AG Robson, GA Wright, PHILIPPE ADRIAAN KESTELYN, GE Holder, AR Webster, FDC Manson, and GCM Black. 2008. “Biallelic Mutation of BEST1 Causes a Distinct Retinopathy in Humans.” American Journal of Human Genetics 82 (1): 19–31.
Vancouver
1.
Burgess R, Millar I, Leroy B, Urquhart J, Fearon I, De Baere E, et al. Biallelic mutation of BEST1 causes a distinct retinopathy in humans. AMERICAN JOURNAL OF HUMAN GENETICS. CAMBRIDGE, MA 02139 USA: CELL PRESS, 600 TECHNOLOGY SQUARE, 5TH FLOOR; 2008;82(1):19–31.
IEEE
[1]
R. Burgess et al., “Biallelic mutation of BEST1 causes a distinct retinopathy in humans,” AMERICAN JOURNAL OF HUMAN GENETICS, vol. 82, no. 1, pp. 19–31, 2008.
@article{520406,
  abstract     = {{We describe a distinct retinal disorder, autosomal-recessive bestrophinopathy (ARB), that is consequent upon biallelic mutation in BEST1 and is associated with central visual loss, a characteristic retinopathy, an absent electro-oculogram light rise, and a reduced electroretinogram. Heterozygous mutations in BEST1 have previously been found to cause the two dominantly inherited disorders, Best macular dystrophy and autosomal-dominant vitreoretinochoroidopathy. The transmembrane protein bestrophin-1, encoded by BEST1, is located at the basolateral membrane of the retinal pigment epithelium in which it probably functions as a Cl- channel. We sequenced BEST1 in five families, identifying DNA variants in each of ten alleles. These encoded six different missense variants and one nonsense variant. The alleles segregated appropriately for a recessive disorder in each family. No clinical or electrophysiological abnormalities were identified in any heterozygotes. We conducted whole-cell patch-clamping of HEK293 cells transfected with bestrophin-1 to measure the Cl- current. Two ARB missense isoforms severely reduced channel activity. However, unlike two other alleles previously associated with Best disease, cotransfection with wild-type bestrophin-1 did not impair the formation of active wild-type bestrophin-1 channels, consistent with the recessive nature of the condition. We propose that ARB is the null phenotype of bestrophin-1 in humans.}},
  author       = {{Burgess, R and Millar, ID and Leroy, Bart and Urquhart, JE and Fearon, IM and De Baere, Elfride and Brown, PD and Robson, AG and Wright, GA and KESTELYN, PHILIPPE ADRIAAN and Holder, GE and Webster, AR and Manson, FDC and Black, GCM}},
  issn         = {{0002-9297}},
  journal      = {{AMERICAN JOURNAL OF HUMAN GENETICS}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{19--31}},
  publisher    = {{CELL PRESS, 600 TECHNOLOGY SQUARE, 5TH FLOOR}},
  title        = {{Biallelic mutation of BEST1 causes a distinct retinopathy in humans}},
  url          = {{http://dx.doi.org/10.1016/j.ajhg.2007.08.004}},
  volume       = {{82}},
  year         = {{2008}},
}

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