Fung Adrian T, Yzer Suzanne, Goldberg Naomi, Wang Hao, Nissen Michael, Giovannini Alfonso, Merriam Joanna E, Bukanova Elena N, Cai Carolyn, Yannuzzi Lawrence A, Tsang Stephen H, Allikmets Rando
*Vitreous-Retina-Macula Consultants of New York and the LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Institute, New York, New York; †Department of Ophthalmology, Columbia University, New York, New York; ‡Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York; §Department of Pathology and Cell Biology, Columbia University, New York, New York; ¶Albany Medical Center, Albany, New York; **Department of Ophthalmology, Weill Cornell Medical College, New York, New York; ††Ophthalmology Section, Department of Neuroscience, Polytechnic University of Marche, Ancona, Italy; ‡‡Australian School of Advanced Medicine, Macquarie University Hospital, Sydney, Australia; and §§Save Sight Institute, University of Sydney, Sydney, Australia.
Retina. 2015 Apr;35(4):773-82. doi: 10.1097/IAE.0000000000000387.
To report the ocular phenotype in patients with autosomal recessive bestrophinopathy and carriers, and to describe novel BEST1 mutations.
Patients with clinically suspected and subsequently genetically proven autosomal recessive bestrophinopathy underwent full ophthalmic examination and investigation with fundus autofluorescence imaging, spectral domain optical coherence tomography, electroretinography, and electrooculography. Mutation analysis of the BEST1 gene was performed through direct Sanger sequencing.
Five affected patients from four families were identified. Mean age was 16 years (range, 6-42 years). All affected patients presented with reduced visual acuity and bilateral, hyperautofluorescent subretinal yellowish deposits within the posterior pole. Spectral domain optical coherence tomography demonstrated submacular fluid and subretinal vitelliform material in all patients. A cystoid maculopathy was seen in all but one patient. In 1 patient, the location of the vitelliform material was seen to change over a follow-up period of 3 years despite relatively stable vision. Visual acuity and fundus changes were unresponsive to topical and systemic carbonic anhydrase inhibitors and systemic steroids. Carriers had normal ocular examinations including normal fundus autofluorescence. Three novel mutations were detected.
Three novel BEST1 mutations are described, suggesting that many deleterious variants in BEST1 resulting in haploinsufficiency are still unknown. Mutations causing autosomal recessive bestrophinopathy are mostly located outside of the exons that usually harbor vitelliform macular dystrophy-associated dominant mutations.
报告常染色体隐性遗传性Bestrophin病患者及其携带者的眼部表型，并描述新的BEST1突变。
对临床疑似且随后经基因证实为常染色体隐性遗传性Bestrophin病的患者进行全面眼科检查，并采用眼底自发荧光成像、光谱域光学相干断层扫描、视网膜电图和眼电图进行检查。通过直接桑格测序对BEST1基因进行突变分析。
确定了来自4个家庭的5名受累患者。平均年龄为16岁（范围6 - 42岁）。所有受累患者均表现为视力下降，后极部双侧视网膜下有高自发荧光的淡黄色沉积物。光谱域光学相干断层扫描显示所有患者均有黄斑下积液和视网膜下卵黄样物质。除1名患者外，所有患者均可见黄斑囊样病变。1名患者在3年的随访期内，尽管视力相对稳定，但卵黄样物质的位置发生了变化。视力和眼底改变对局部和全身碳酸酐酶抑制剂及全身类固醇治疗无反应。携带者的眼部检查正常，包括正常的眼底自发荧光。检测到3个新突变。
描述了3个新的BEST1突变，提示导致单倍体不足的BEST1中许多有害变异仍不为人知。导致常染色体隐性遗传性Bestrophin病的突变大多位于通常携带卵黄样黄斑营养不良相关显性突变的外显子之外。
