Yamada Rika, Takagi Rina, Iwamoto Sadahiko, Shimada Shoichi, Kakehashi Akihiro
Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Taiwan J Ophthalmol. 2021 Jan 7;11(1):71-76. doi: 10.4103/tjo.tjo_37_20. eCollection 2021 Jan-Mar.
Autosomal recessive bestrophinopathy (ARB) is a disease that results from the mutations in the gene. It is characterized by multifocal yellowish lipofuscin deposits, cystoid macular edema, and subretinal fluid. Among approximately 270 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 mutations and describe the genotype-phenotype relationship in Japanese dizygotic twins presenting with ARB.
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.
In this study, we have reported on a novel mutation, the p. Phe151Cys mutation, associated with ARB in Japanese dizygotic twins who had bi-allelic p. Ala160Pro mutations in . 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.
It was indicated that the novel 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.
常染色体隐性遗传性Bestrophin病（ARB）是一种由该基因突变导致的疾病。其特征为多灶性淡黄色脂褐素沉着、黄斑囊样水肿和视网膜下液。在大约270种突变中，只有40种（包括杂合突变和纯合突变）与ARB相关。然而，在日本人群中，与ARB相关的突变报道极少。因此，在本研究中，我们旨在鉴定日本双卵双胞胎ARB患者中的突变，并描述其基因型与表型的关系。
我们对患有ARB的日本双卵双胞胎患者（男性，29岁）进行了临床检查，并对这对双胞胎的7名家庭成员进行了全外显子组测序。
在本研究中，我们报道了一种新的突变，即p.Phe151Cys突变，该突变与日本双卵双胞胎的ARB相关，这些双胞胎在基因中存在双等位基因p.Ala160Pro突变。观察到的临床特征为双眼眼底异常，如多灶性淡黄色视网膜下沉着、黄斑囊样水肿和视网膜下液。全视野视网膜电图结果低于正常。
表明所鉴定的新突变可能与双眼ARB密切相关。本研究为日本ARB患者的基因型-表型关联提供了重要信息。此外，我们进行的基因分析对鉴别诊断非常有用，可能对未来治疗方法的开发有启示意义。
