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High-resolution photoreceptor imaging analysis of patients with autosomal dominant retinitis pigmentosa (adRP) caused by HK1 mutation.
Ophthalmic Genetics ( IF 1.2 ) Pub Date : 2020-08-20 , DOI: 10.1080/13816810.2020.1810284
Daiki Kubota 1 , Kaori Matsumoto 1, 2 , Mika Hayashi 1 , Noriko Oishi 1 , Kiyoko Gocho 1, 3 , Kunihiko Yamaki 1 , Shinichiro Kobayakawa 4 , Tsutomu Igarashi 2 , Hiroshi Takahashi 2 , Shuhei Kameya 1
Affiliation  

ABSTRACT

Purpose

The hexokinase 1 (HK1) gene encodes one of the four human hexokinases that play essential roles in glucose metabolism. Recently, several cases of E847K mutation in the HK1 gene were reported to cause inherited retinal dystrophy. The purpose of this study was to identify the phenotypical characteristics of patients with a recurrent E847K mutation in the HK1 gene.

Methods

Three generations of one family with autosomal dominant retinitis pigmentosa were examined. Whole exome sequencing was performed on the DNA. Fundus imaging by an adaptive optics fundus camera was used to obtain high-resolution photoreceptor images.

Results

Fundus examination of the proband showed degeneration of the mid-peripheral retina, and SD-OCT images showed an absence of the ellipsoid zone (EZ) and interdigitation zone (IZ) in the parafovea and more peripherally. SD-OCT images of the mother of the proband showed an absence of the EZ and IZ, and fundus autofluorescence images showed hypo-autofluorescence surrounding the macular region. One daughter of the proband had only mild night blindness, however, the density of the cone photoreceptors was reduced in the parafoveal region. Whole exome sequencing identified a heterozygous variant, E847K, in the HK1 gene. This variant was found to co-segregate with the disease in three family members.

Conclusions

Although the systemic phenotypes were found to be associated with the HK1 mutations, only the E847K mutation can cause a non-syndromic photoreceptor degeneration. Our study strengthened the hypothesis that the amino acid E847 might play a critical role in the maintenance of the morphology and function of the photoreceptors.



中文翻译:

由HK1突变引起的常染色体显性遗传性视网膜色素变性(adRP)患者的高分辨率感光成像分析。

摘要

目的

己糖激酶1(HK1)基因编码在葡萄糖代谢中起重要作用的四种人类己糖激酶之一。最近,据报道,HK1基因中有几例E847K突变引起遗传性视网膜营养不良。这项研究的目的是确定HK1基因中复发性E847K突变的患者的表型特征。

方法

研究了一个常染色体显性遗传性视网膜色素变性的家庭的三代人。对DNA进行了整个外显子组测序。自适应光学眼底照相机的眼底成像用于获得高分辨率的感光体图像。

结果

先证者的眼底检查显示中周视网膜变性,SD-OCT图像显示在副凹及周边更多的区域没有椭圆体区(EZ)和指间区(IZ)。先证者母亲的SD-OCT图像显示EZ和IZ缺失,眼底自发荧光图像显示黄斑区域周围的自发荧光不足。先证者的一个女儿只有轻度的夜盲症,但是,在中央凹旁区域,锥体感光体的密度降低了。整个外显子组测序鉴定出HK1基因中的杂合变异体E847K 。发现该变体与该疾病在三个家庭成员中共隔离。

结论

尽管发现系统表型与HK1突变有关,但只有E847K突变可以引起非综合征性感光受体的变性。我们的研究强化了以下假设:氨基酸E847可能在维持感光器的形态和功能中起关键作用。

更新日期:2020-08-20
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