A novel phenotype in a family with autosomal dominant retinal dystrophy due to c.1430A > G in retinoid isomerohydrolase ( RPE65 ) and c.37C > T in bestrophin 1 ( BEST1 ),Documenta Ophthalmologica

当前位置： X-MOL 学术 › Doc. Ophthalmol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

A novel phenotype in a family with autosomal dominant retinal dystrophy due to c.1430A > G in retinoid isomerohydrolase ( RPE65 ) and c.37C > T in bestrophin 1 ( BEST1 )
Documenta Ophthalmologica ( IF 2.6 ) Pub Date : 2021-01-29 , DOI: 10.1007/s10633-021-09819-x
Juanita Pappalardo ₁ , Rachael C Heath Jeffery _{1,

2} , Jennifer A Thompson ₃ , Enid Chelva ₃ , Quang Pham ₁ , Ian J Constable ₁ , Terri L McLaren _{1,

3} , Tina M Lamey _{1,

3} , John N De Roach _{1,

3} , Fred K Chen _{1,

2,

3,

4}

Affiliation

Purpose

The c.1430A > G (Asp477Gly) variant in RPE65 has been reported in Irish and Scottish families with either an autosomal dominant retinal dystrophy (adRD) that resembles choroideremia, a vitelliform macular dystrophy or an isolated macular atrophy. We report novel features on multimodal imaging and the natural history of a family harbouring this variant in combination with the BEST1 c.37C > T (Arg13Cys) variant.

Methods

Members of a family with an adRD were examined clinically to ascertain phenotype and underwent genetic testing. Multimodal imaging included widefield colour fundus photography, quantitative autofluorescence (qAF) and spectral domain optical coherence tomography. Electrophysiology and microperimetry were also performed.

Results

Vision loss was attributed to foveal atrophy in the proband and choroidal neovascularisation and a vitello-eruptive lesion in one affected son. Peripheral retinal white dots corresponding to subretinal deposits were seen in three patients. The median qAF₈ values in the proband (I:1) were low (40 and 101 in OD and OS) at age 79. Similarly, the qAF₈ values for the middle son (II:2) were also low (100 and 87 in ODS and OS) at age 60. Electrophysiology showed disproportionate reduction in Arden ratio prior to the gradual loss of full-field responses. Microperimetry demonstrated an enlarging scotoma in the proband.

Conclusions

The coexistence of the pathogenic BEST1 c.37C > T variant may modify clinical features observed in RPE65 adRD. This study expands our understanding of RPE65 adRD as a retinoid cycle disorder supported by the reduced qAF, fine white retinal dots and corresponding subretinal deposits on OCT in affected members.

中文翻译：

由于类视黄醇异构水解酶 ( RPE65 ) 中 c.1430A > G 和 bestrophin 1 ( BEST1 ) 中 c.37C > T 导致的常染色体显性视网膜营养不良家族的新表型

目的

RPE65中的 c.1430A > G (Asp477Gly) 变体已在爱尔兰和苏格兰家族中报道，其具有类似于脉络膜血症的常染色体显性视网膜营养不良 (adRD)、卵黄状黄斑营养不良或孤立性黄斑萎缩。我们结合BEST1 c.37C > T (Arg13Cys) 变体报告了多模态成像的新特征以及携带该变体的家族的自然史。

方法

对患有 adRD 的家庭成员进行临床检查以确定表型并进行基因检测。多模态成像包括宽场彩色眼底摄影、定量自发荧光 (qAF) 和光谱域光学相干断层扫描。还进行了电生理学和微观测量。

结果

视力丧失归因于先证者的中心凹萎缩和脉络膜新生血管形成以及一名受影响儿子的卵黄发疹病变。在三名患者中观察到与视网膜下沉积物相对应的周围视网膜白点。先证者 (I:1)的中位 qAF ₈值在 79 岁时较低（OD 和 OS 分别为 40 和 101）。同样，中间儿子 (II:2) 的 qAF ₈值也较低（100 和 87在 ODS 和 OS 中）在 60 岁时。在全场反应逐渐丧失之前，电生理学显示 Arden 比率不成比例地降低。显微视野检查显示先证者有扩大的暗点。