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Gene Review

BEST1  -  bestrophin 1

Homo sapiens

Synonyms: ARB, BEST, BMD, Bestrophin-1, RP50, ...
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Disease relevance of BEST1


Psychiatry related information on BEST1

  • FM and extracellular-to-intracellular-water ratio were measured by bromide-deuterium dilution, BMD by dual-energy x-ray absorptiometry, GH function by fasted serum insulin-like growth factor-I concentration, and physical activity by doubly-labeled water in combination with basal metabolic rate by a ventilated hood [6].
  • Change in Lumbar Spine BMD and Vertebral Fracture Risk Reduction in Teriparatide-Treated Postmenopausal Women With Osteoporosis* [7].
  • After adjustment for CC, age, weight, alcohol consumption, and cigarette smoking, high PA compared with medium or low PA was associated with higher hip BMD and heel QUS (total hip BMD, 3.1%; p < 0.001; QUS stiffness, 2.7%; p = 0.002) [8].
  • INTRODUCTION:: Prevalence estimates of osteopenia and osteoporosis (reduced bone mineral density; BMD) in HIV-infected patients and the role of antiretroviral therapy (ART) varies in the literature [9].
  • 1. Best-subset regression analysis and receiver operating characteristic analysis were used to select a subset of items from the structured interview that most efficiently predicted PTSD as diagnosed in the full-length interview [10].

High impact information on BEST1

  • Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), a much milder form of the disease where the age of onset can sometimes be as late as the third or fourth decade of life, are caused by mutations in the same X-linked gene, a 14 kilobase (kb) transcript which is spread over more than 2 megabases of the human X chromosome [11].
  • Most mutations causing DMD and BMD are deletions and deletions associated with both phenotypes are observed throughout the gene sequence [11].
  • This observation led to the suggestion that DMD patients possess deletions that disrupt the reading frame of the protein, whereas BMD patients have deletions that retain the translational reading frame and enable the muscle cells to produce altered dystrophin products [11].
  • This theory is supported by immunoblotting studies, which show that DMD patients lack dystrophin in their muscle cells or that dystrophin is present at very low levels, whereas BMD patients produce a protein with reduced abundance or abnormal size [11].
  • Here we describe a deletion of the dystrophin gene in a family segregating for very mild BMD, one member of which was still ambulant at age 61 years, which removes a central part of the dystrophin gene encompassing 5,106 base pairs of coding sequence, almost half the coding information [11].

Chemical compound and disease context of BEST1

  • Interaction analyses with years since menopause, estrogen status, physical activity, smoking, dietary calcium, vitamin D, and alcohol intake were based on BMD measurements at the hip [12].
  • CONCLUSIONS: Oral alendronate increases BMD and increase nonsevere gastrointestinal adverse effects but does not modify the hearing loss in adult patients with osteogenesis imperfecta [13].
  • In the univariate analysis, significant interactions were observed between raloxifene treatment and age (p = 0.04), serum triglycerides (p = 0.03), LS BMD (p = 0.08), and diabetes mellitus (p = 0.04) [14].
  • 25-Hydroxyvitamin D Deficiency and Diabetes Predict Reduced BMD in Patients With Chronic Kidney Disease [15].
  • MATERIALS AND METHODS: This prospectively designed subprotocol (n = 308) of ATAC assessed changes in BMD and bone turnover markers in postmenopausal women with invasive primary breast cancer receiving anastrozole 1 mg/day, tamoxifen 20 mg/day, or combination treatment with both agents for 5 years [16].

Biological context of BEST1


Anatomical context of BEST1


Associations of BEST1 with chemical compounds

  • RESULTS: A single T to G transition at nucleotide 663 was identified in one of the VMD2 gene copies of the patient, which results in a Cys to Trp substitution at position 221 in the corresponding protein (C221W) [3].
  • Thus, Ca(2+) appears to activate the bestrophin Cl(-) channel without going through a freely diffusible messenger or through protein phosphorylation [20].
  • Hydrodynamic properties of porcine bestrophin-1 in Triton X-100 [24].
  • METHODS: Patients with VMD2 were imaged with conventional fundus and autofluorescence photography, fluorescein angiography, fundus photography, and optical coherence tomography (OCT) [25].
  • Using heterologous expression, we show here that human, Drosophila, and C. elegans bestrophins form oligomeric chloride channels, and that human bestrophin is sensitive to intracellular calcium [26].

Other interactions of BEST1

  • MITF knockdown by small interfering RNA (siRNA) in cell culture revealed a strong correlation between MITF and VMD2 mRNA levels [27].
  • Best's vitelliform dystrophy (VMD2) maps between D11S903 and PYGM: no evidence for locus heterogeneity [28].
  • Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC) [29].
  • The data showed that VMD2 mutations caused defects of ocular patterning, supporting the hypothesized role for the RPE, and specifically VMD2, in the normal growth and development of the eye [29].
  • Recombination events localized the disease gene to the 5-cM interval D11S956-UGB, a genetic inclusion interval that substantially overlaps the VMD2 inclusion interval defined by recombinants at FCER1B and UGB observed by other research groups [30].

Analytical, diagnostic and therapeutic context of BEST1


  1. Identification of the gene responsible for Best macular dystrophy. Petrukhin, K., Koisti, M.J., Bakall, B., Li, W., Xie, G., Marknell, T., Sandgren, O., Forsman, K., Holmgren, G., Andreasson, S., Vujic, M., Bergen, A.A., McGarty-Dugan, V., Figueroa, D., Austin, C.P., Metzker, M.L., Caskey, C.T., Wadelius, C. Nat. Genet. (1998) [Pubmed]
  2. Single cl- channels activated by Ca2+ in Drosophila s2 cells are mediated by bestrophins. Chien, L.T., Zhang, Z.R., Hartzell, H.C. J. Gen. Physiol. (2006) [Pubmed]
  3. A novel spontaneous missense mutation in VMD2 gene is a cause of a best macular dystrophy sporadic case. Palomba, G., Rozzo, C., Angius, A., Pierrottet, C.O., Orzalesi, N., Pirastu, M. Am. J. Ophthalmol. (2000) [Pubmed]
  4. Do "America's Best Hospitals" perform better for acute myocardial infarction? Chen, J., Radford, M.J., Wang, Y., Marciniak, T.A., Krumholz, H.M. N. Engl. J. Med. (1999) [Pubmed]
  5. A cDNA clone from the Duchenne/Becker muscular dystrophy gene. Burghes, A.H., Logan, C., Hu, X., Belfall, B., Worton, R.G., Ray, P.N. Nature (1987) [Pubmed]
  6. Body composition in Prader-Willi syndrome compared with nonsyndromal obesity: Relationship to physical activity and growth hormone function. van Mil, E.G., Westerterp, K.R., Gerver, W.J., Van Marken Lichtenbelt, W.D., Kester, A.D., Saris, W.H. J. Pediatr. (2001) [Pubmed]
  7. Change in Lumbar Spine BMD and Vertebral Fracture Risk Reduction in Teriparatide-Treated Postmenopausal Women With Osteoporosis*. Chen, P., Miller, P.D., Delmas, P.D., Misurski, D.A., Krege, J.H. J. Bone Miner. Res. (2006) [Pubmed]
  8. Physical activity and calcium consumption are important determinants of lower limb bone mass in older women. Devine, A., Dhaliwal, S.S., Dick, I.M., Bollerslev, J., Prince, R.L. J. Bone Miner. Res. (2004) [Pubmed]
  9. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. Brown, T.T., Qaqish, R.B. AIDS (2006) [Pubmed]
  10. Short screening scale for DSM-IV posttraumatic stress disorder. Breslau, N., Peterson, E.L., Kessler, R.C., Schultz, L.R. The American journal of psychiatry. (1999) [Pubmed]
  11. Very mild muscular dystrophy associated with the deletion of 46% of dystrophin. England, S.B., Nicholson, L.V., Johnson, M.A., Forrest, S.M., Love, D.R., Zubrzycka-Gaarn, E.E., Bulman, D.E., Harris, J.B., Davies, K.E. Nature (1990) [Pubmed]
  12. Interactions of interleukin-6 promoter polymorphisms with dietary and lifestyle factors and their association with bone mass in men and women from the Framingham Osteoporosis Study. Ferrari, S.L., Karasik, D., Liu, J., Karamohamed, S., Herbert, A.G., Cupples, L.A., Kiel, D.P. J. Bone Miner. Res. (2004) [Pubmed]
  13. Effects of oral alendronate on BMD in adult patients with osteogenesis imperfecta: a 3-year randomized placebo-controlled trial. Chevrel, G., Schott, A.M., Fontanges, E., Charrin, J.E., Lina-Granade, G., Duboeuf, F., Garnero, P., Arlot, M., Raynal, C., Meunier, P.J. J. Bone Miner. Res. (2006) [Pubmed]
  14. Associations between baseline risk factors and vertebral fracture risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study. Johnell, O., Kanis, J.A., Black, D.M., Balogh, A., Poor, G., Sarkar, S., Zhou, C., Pavo, I. J. Bone Miner. Res. (2004) [Pubmed]
  15. 25-Hydroxyvitamin D Deficiency and Diabetes Predict Reduced BMD in Patients With Chronic Kidney Disease. Elder, G.J., Mackun, K. J. Bone Miner. Res. (2006) [Pubmed]
  16. Effect of an aromatase inhibitor on bmd and bone turnover markers: 2-year results of the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial (18233230). Eastell, R., Hannon, R.A., Cuzick, J., Dowsett, M., Clack, G., Adams, J.E. J. Bone Miner. Res. (2006) [Pubmed]
  17. Analysis of the VMD2 promoter and implication of E-box binding factors in its regulation. Esumi, N., Oshima, Y., Li, Y., Campochiaro, P.A., Zack, D.J. J. Biol. Chem. (2004) [Pubmed]
  18. High-resolution meiotic and physical mapping of the best vitelliform macular dystrophy (VMD2) locus to pericentromeric chromosome 11. Weber, B.H., Vogt, G., Stöhr, H., Sander, S., Walker, D., Jones, C. Am. J. Hum. Genet. (1994) [Pubmed]
  19. Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies. Allikmets, R., Seddon, J.M., Bernstein, P.S., Hutchinson, A., Atkinson, A., Sharma, S., Gerrard, B., Li, W., Metzker, M.L., Wadelius, C., Caskey, C.T., Dean, M., Petrukhin, K. Hum. Genet. (1999) [Pubmed]
  20. Ca2+-activated Cl- current from human bestrophin-4 in excised membrane patches. Tsunenari, T., Nathans, J., Yau, K.W. J. Gen. Physiol. (2006) [Pubmed]
  21. Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium. Marmorstein, A.D., Marmorstein, L.Y., Rayborn, M., Wang, X., Hollyfield, J.G., Petrukhin, K. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  22. The role of bestrophin in airway epithelial ion transport. Duta, V., Szkotak, A.J., Nahirney, D., Duszyk, M. FEBS Lett. (2004) [Pubmed]
  23. Body composition assessment in spinal cord injury subjects. Maggioni, M., Bertoli, S., Margonato, V., Merati, G., Veicsteinas, A., Testolin, G. Acta diabetologica. (2003) [Pubmed]
  24. Hydrodynamic properties of porcine bestrophin-1 in Triton X-100. Stanton, J.B., Goldberg, A.F., Hoppe, G., Marmorstein, L.Y., Marmorstein, A.D. Biochim. Biophys. Acta (2006) [Pubmed]
  25. Vitelliform macular dystrophy. Spaide, R.F., Noble, K., Morgan, A., Freund, K.B. Ophthalmology (2006) [Pubmed]
  26. The vitelliform macular dystrophy protein defines a new family of chloride channels. Sun, H., Tsunenari, T., Yau, K.W., Nathans, J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  27. VMD2 promoter requires two proximal E-box sites for its activity in vivo and is regulated by the MITF-TFE family. Esumi, N., Kachi, S., Campochiaro, P.A., Zack, D.J. J. Biol. Chem. (2007) [Pubmed]
  28. Best's vitelliform dystrophy (VMD2) maps between D11S903 and PYGM: no evidence for locus heterogeneity. Weber, B.H., Walker, D., Müller, B., Mar, L. Genomics (1994) [Pubmed]
  29. Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC). Yardley, J., Leroy, B.P., Hart-Holden, N., Lafaut, B.A., Loeys, B., Messiaen, L.M., Perveen, R., Reddy, M.A., Bhattacharya, S.S., Traboulsi, E., Baralle, D., De Laey, J.J., Puech, B., Kestelyn, P., Moore, A.T., Manson, F.D., Black, G.C. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  30. Linkage study of Best's vitelliform macular dystrophy (VMD2) in a large North American family. Hou, Y.C., Richards, J.E., Bingham, E.L., Pawar, H., Scott, K., Segal, M., Lunetta, K.L., Boehnke, M., Sieving, P.A. Hum. Hered. (1996) [Pubmed]
  31. Phenotype and genotype correlations in two best families. Seddon, J.M., Sharma, S., Chong, S., Hutchinson, A., Allikmets, R., Adelman, R.A. Ophthalmology (2003) [Pubmed]
  32. Use of denaturing HPLC and automated sequencing to screen the VMD2 gene for mutations associated with Best's vitelliform macular dystrophy. Marchant, D., Gogat, K., Dureau, P., Sainton, K., Sternberg, C., Gadin, S., Dollfus, H., Brasseur, G., Hache, J.C., Dumur, V., Puech, V., Munier, F., Schorderet, D.F., Marsac, C., Menasche, M., Dufier, J.L., Abitbol, M. Ophthalmic Genet. (2002) [Pubmed]
  33. Sustained expression after nonviral ocular gene transfer using mammalian promoters. Kachi, S., Esumi, N., Zack, D.J., Campochiaro, P.A. Gene Ther. (2006) [Pubmed]
  34. Evidence of genetic heterogeneity in MRCS (microcornea, rod-cone dystrophy, cataract, and posterior staphyloma) syndrome. Michaelides, M., Urquhart, J., Holder, G.E., Restori, M., Kayali, N., Manson, F.D., Black, G.C. Am. J. Ophthalmol. (2006) [Pubmed]
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