Zhi-Hong Zhu, Xin Jin, Yi-Xin Zhang, Rui Wang, Tong Wu, Wei Liu, Ze-Hua Chen, Hai-Nan Xie, Lan-Lan Chen, Zi-Hao Liu, Hou-Bin Huang | International Journal Ophthalmology | 2022 Feb 18 | 15(2) | pages 205–212 | doi:10.18240/ijo.2022.02.03
AIM
To describe the clinical heterogeneity of patients with novel mutations in BEST1.
METHODS
All the members in the two Chinese families underwent detailed clinical evaluations including best-corrected visual acuity, slit-lamp examination, applanation tonometry, and dilated fundus examination. Fundus autofluorescence, fundus fluorescein angiography, spectral-domain optical coherence tomography, electrooculography, and electroretinogram were also performed. Genomic DNA was extracted from venous blood for all the participants. The targeted next-generation sequencing of inherited retinal disease-associated genes was conducted to identify the causative mutation.
RESULTS
A novel BEST1 missense mutation c.41T>C (p.Leu14Ser) was identified in Family 1. It was co-segregated with the phenotype of best vitelliform macular dystrophy (BVMD) and bioinformatics analysis confirmed it was harmful. Another novel BEST1 frameshift mutation c.345_346insGGCAAGGACG (p.Glu119Glyfs*116) and a novel USH2A missense mutation c.12560G>A, p.Arg4187His were identified in family 2 with retinitis pigmentosa (RP), which might interact and lead to the phenotype of RP.
CONCLUSION
Two novel mutations in the BEST1 gene in two unrelated families with distinct phenotypes and BEST1 mutation accompanied with USH2A mutation would result in RP, which could be enormously helpful in understanding the pathogenesis of the inherited retinal disease caused by a BEST1 mutation.
Reference
Johnson AA, Guziewicz KE, Lee CJ, Kalathur RC, Pulido JS, Marmorstein LY, Marmorstein AD. Bestrophin 1 and retinal disease. Prog Retin Eye Res 2017;58:45-69.<br&#x003E
Lin Y, Li T, Gao HB, Lian Y, Chen C, Zhu Y, Li YH, Liu BQ, Zhou WL, Jiang HY, Liu XL, Zhao XJ, Liang XL, Jin CJ, Huang XH, Lu L. Bestrophin 1 gene analysis and associated clinical findings in a Chinese patient with Best vitelliform macular dystrophy. Mol Med Rep 2017;16(4):4751-4755.<br&#x003E
Smith JJ, Nommiste B, Carr AJF. Bestrophin1: a gene that causes many diseases. Adv Exp Med Biol 2019;1185:419-423.<br&#x003E
Marmorstein AD, Johnson AA, Bachman LA, Andrews-Pfannkoch C, Knudsen T, Gilles BJ, Hill M, Gandhi JK, Marmorstein LY, Pulido JS. Mutant BEST1 expression and impaired phagocytosis in an iPSC model of autosomal recessive bestrophinopathy. Sci Rep 2018;8:4487.<br&#x003E
Marmorstein AD, Kinnick TR, Stanton JB, Johnson AA, Lynch RM, Marmorstein LY. Bestrophin-1 influences transepithelial electrical properties and Ca2+ signaling in human retinal pigment epithelium. Mol Vis 2015;21:347-359.<br&#x003E
Gao TT, Tian CQ, Xu H, Tang X, Huang LZ, Zhao MW. Disease-causing mutations associated with bestrophinopathies promote apoptosis in retinal pigment epithelium cells. Graefes Arch Clin Exp Ophthalmol 2020;258(10):2251-2261.<br&#x003E
Katagiri S, Hayashi T, Ohkuma Y, Sekiryu T, Takeuchi T, Gekka T, Kondo M, Iwata T, Tsuneoka H. Mutation analysis of BEST1 in Japanese patients with Best's vitelliform macular dystrophy. Br J Ophthalmol 2015;99(11):1577-1582.<br&#x003E
Guziewicz KE, Sinha D, Gómez NM, Zorych K, Dutrow EV, Dhingra A, Mullins RF, Stone EM, Gamm DM, Boesze-Battaglia K, Aguirre GD. Bestrophinopathy: an RPE-photoreceptor interface disease. Prog Retin Eye Res 2017;58:70-88.<br&#x003E
Fister TA, Zein WM, Cukras CA, Sen HN, Maldonado RS, Huryn LA, Hufnagel RB. Phenotypic and genetic spectrum of autosomal recessive bestrophinopathy and best vitelliform macular dystrophy. Invest Ophthalmol Vis Sci 2021;62(6):22.<br>
Best F. Über eine hereditäre Maculaaffektion. Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde 1905;13(3):199-212.<br&#x003E
Lin Y, Li T, Ma CH, Gao HB, Chen C, Zhu Y, Liu BQ, Lian Y, Huang Y, Li HC, Wu QX, Liang XL, Jin CJ, Huang XH, Ye JH, Lu L. Genetic variations in Bestrophin1 and associated clinical findings in two Chinese patients with juvenileonset and adultonset best vitelliform macular dystrophy. Mol Med Rep 2018;17(1):225-233.<br&#x003E
sang SH, Sharma T. Best vitelliform macular dystrophy. Adv Exp Med Biol 2018;1085:79-90.<br&#x003E
Parodi MB, Arrigo A, Bandello F. Reply: natural course of the vitelliform stage in best vitelliform macular dystrophy: a five-year follow-up study. Graefes Arch Clin Exp Ophthalmol 2021;259(3):789-790.<br&#x003E
Burgess R, Millar ID, Leroy BP, Urquhart JE, Fearon IM, De Baere E, Brown PD, Robson AG, Wright GA, Kestelyn P, Holder GE, Webster AR, Manson FD, Black GC. Biallelic mutation of BEST1 causes a distinct retinopathy in humans. Am J Hum Genet 2008;82(1):19-31.<br&#x003E
Kaufman SJ, Goldberg MF, Orth DH, Fishman GA, Tessler H, Mizuno K. Autosomal dominant vitreoretinochoroidopathy. Arch Ophthalmol 1982;100(2):272-278.<br&#x003E
Davidson AE, Millar ID, Urquhart JE, Burgess-Mullan R, Shweikh Y, Parry N, O'Sullivan J, Maher GJ, McKibbin M, Downes SM, Lotery AJ, Jacobson SG, Brown PD, Black GCM, Manson FDC. Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa. Am J Hum Genet 2009;85(5):581-592.<br&#x003E
Dalvin LA, Abou Chehade JE, Chiang J, Fuchs J, Iezzi R, Marmorstein AD. Retinitis pigmentosa associated with a mutation in BEST1. Am J Ophthalmol Case Rep 2016;2:11-17.<br&#x003E
Li H, Durbin R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 2010;26(5):589-595.<br&#x003E
Wang K, Li MY, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010;38(16):e164.<br&#x003E
Auton A, Abecasis GR, Altshuler DM, et al. A global reference for human genetic variation. Nature 2015;526(7571):68-74.<br&#x003E
Jin X, Chen LL, Wang DJ, Zhang YX, Chen ZH, Huang HB. Novel compound heterozygous mutation in the POC1B gene underlie peripheral cone dystrophy in a Chinese family. Ophthalmic Genet 2018;39(3):300-306.<br&#x003E
Jin X, Liu W, Qv LH, Huang HB. A novel variant in PAX6 as the cause of aniridia in a Chinese family. BMC Ophthalmol 2021;21(1):225.<br&#x003E
Jin X, Qu LH, Hou BK, Xu HW, Meng XH, Pang CP, Yin ZQ. Novel compound heterozygous mutation in the CNGA1 gene underlie autosomal recessive retinitis pigmentosa in a Chinese family. Biosci Rep 2016;36(1):e00289.<br&#x003E
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, Committee ACMGLQA. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17(5):405-424.<br&#x003E
Ji CY, Li Y, Kittredge A, Hopiavuori A, Ward N, Yao P, Fukuda Y, Zhang Y, Tsang SH, Yang TT. Investigation and restoration of BEST1 activity in patient-derived RPEs with dominant mutations. Sci Rep 2019;9(1):19026.<br&#x003E
Owji AP, Kittredge A, Zhang Y, Yang TT. Structure and Function of the Bestrophin family of calcium-activated chloride channels. Channels (Austin) 2021;15(1):604-623.<br&#x003E
Uggenti C, Briant K, Streit AK, Thomson S, Koay YH, Baines RA, Swanton E, Manson FD. Restoration of mutant bestrophin-1 expression, localisation and function in a polarised epithelial cell model. Dis Model Mech 2016;9(11):1317-1328.<br&#x003E
Singh R, Kuai D, Guziewicz KE, Meyer J, Wilson M, Lu JF, Smith M, Clark E, Verhoeven A, Aguirre GD, Gamm DM. Pharmacological modulation of photoreceptor outer segment degradation in a human iPS cell model of inherited macular degeneration. Mol Ther 2015 23(11):1700-1711.<br&#x003E
Gao TT, Tian CQ, Hu QR, Liu ZM, Zou JM, Huang LZ, Zhao MW. Clinical and mutation analysis of patients with best vitelliform macular dystrophy or autosomal recessive bestrophinopathy in Chinese population. Biomed Res Int 2018;2018:4582816.<br&#x003E
Guziewicz KE, Cideciyan AV, Beltran WA, Komáromy AM, Dufour VL, Swider M, Iwabe S, Sumaroka A, Kendrick BT, Ruthel G, Chiodo VA, Héon E, Hauswirth WW, Jacobson SG, Aguirre GD. BEST1 gene therapy corrects a diffuse retina-wide microdetachment modulated by light exposure. Proc Natl Acad Sci U S A 2018;115(12): E2839-E2848.<br&#x003E
Singh Grewal S, Smith JJ, Carr AJF. Bestrophinopathies: perspectives on clinical disease, Bestrophin-1 function and developing therapies. Ther Adv Ophthalmol 2021;13:2515841421997191.
Comments