Analysis of BEST1 mutations and clinical features in Chinese patients with multifocal vitelliform retinopathy

Abstract

Purpose : Multifocal vitelliform retinopathy (MVR) is featured by multifocal vitelliform deposits under retina and reduced electrooculography (EOG) light rise. About 60% MVR patients carry heterozygous mutation in BEST1 gene. Few studies analyze MVR in Chinese population. The purpose of the study is to analyze the BEST1 mutations and clinical features in Chinese patients with MVR.

Methods : Five MVR families, including 9 patients and 10 healthy family members were recruited. Coding exons and flanking intronic regions of BEST1 were amplified by PCR and analyzed by Sanger sequencing. Detailed clinical evaluations were performed in all patients.

Results : All MVR patients carried heterozygous mutation in BEST1 gene. Three missense mutations and 1 deletion mutation were identified, including two novel mutations (p.R47L and p.I78F) (Fig.1). Best-corrected visual acuity ranged from hand motion to 20/20. Mean intraocular pressure was 30.39±11.86 mmHg. All patients showed serous retinal detachment, subretinal vitelliform deposits which had high autofluorescence and reduced EOG light rise. Mean axial length was 21.87±0.63 mm. Ultrasound biomicroscopy revealed narrow or closed chamber angle in 8 patients and shallow central anterior chamber depth (2.17±0.29 mm). Visual field showed defects varied from paracentral scotoma to diffuse defects (Fig.2). Six patients had angle-closure glaucoma (ACG) and 2 patients had angle closure (AC). Genetic testing and clinical examination were normal in 10 family members.

Conclusions : Four mutations with potential functional consequences were identified in BEST1 in a cohort of Chinese MVR patients with high rate of AC and ACG, suggesting a potential genetic and phenomic diversity of MVR in Chinese patients.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Fig.1 Pedigrees of 5 MVR families with BEST1 mutations. * indicates family members who were neither clinically nor genetically examined. † indicates family members who were clinically normal but not genetically examined.

 

Fig.2 Clinical and genetic results of Patient 4,II:1. 2A, fundus photograph revealed increased C/D and scattered vitelliform lesions; 2B, autofluorescence image showed the corresponding lesions had high autofluorescence; 2C-2D, OCT found edema retina, serous retinal detachment and thinned retinal nerve fiber layer; 2E, UBM showed closed chamber angle; 2F, visual field demonstrated diffuse defects; 2G, sequence map showed allelic mutation in BEST1.