Novel BEST1 mutation in autosomal recessive bestrophinopathy in Japanese siblings
Rika Yamada1, Rina Takagi2, Sadahiko Iwamoto3, Shoichi Shimada4, Akihiro Kakehashi2
1 Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka; Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, Saitama, Japan
2 Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, Saitama, Japan
3 Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
4 Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita; Addiction Research Unit, Development of Novel Diagnosis and Treatment Division, Osaka Psychiatric Research Center, Osaka Psychiatric Medical Center,Osaka Prefectural Hospital Organization, Otemae, Chuo-ku, Osaka, Japan
Dr. Akihiro Kakehashi
Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama 330-8503
Source of Support: None, Conflict of Interest: None
PURPOSE: Autosomal recessive bestrophinopathy (ARB) is a disease that results from the mutations in the BEST1 gene. It is characterized by multifocal yellowish lipofuscin deposits, cystoid macular edema, and subretinal fluid. Among approximately 270 BEST1 mutations, only 40 that include both heterozygous and homozygous mutations are associated with ARB. However, very few ARB-related mutations have been reported in the Japanese population. Therefore, in this study, we aimed to identify BEST1 mutations and describe the genotype–phenotype relationship in Japanese dizygotic twins presenting with ARB.
MATERIALS AND METHODS: We performed clinical examinations in Japanese dizygotic twin patients (male: 29 years) with ARB as well as whole-exome sequencing in seven family members of these twins.
RESULTS: In this study, we have reported on a novel BEST1 mutation, the p. Phe151Cys mutation, associated with ARB in Japanese dizygotic twins who had bi-allelic p. Ala160Pro mutations in BEST1. The clinical features observed were binocular abnormalities of the fundus, such as multifocal yellowish subretinal deposits, cystoid macular edema, and subretinal fluid. The full-field electroretinography results were subnormal.
CONCLUSION: It was indicated that the novel BEST1 mutations identified may be strongly correlated with binocular ARB. This study provides significant information of the genotype–phenotype association in Japanese ARB patients. Further, the genetic analysis that we performed was very useful for the differential diagnosis and might have implications in the development of future treatment modalities.