Al-Khuzaei Saoud, Hudspith Karl A Z, Broadgate Suzanne, Shanks Morag E, Clouston Penny, Németh Andrea H, Halford Stephanie, Downes Susan M
Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Oxford Eye Hospital, John Radcliffe Hospital, Headley Way, Oxford, OX9 3DU, UK.
BMC Ophthalmol. 2021 Apr 9;21(1):168. doi: 10.1186/s12886-021-01919-1.
We present 3 members of a family with macular dystrophy, originally diagnosed as Stargardt disease, with a significantly variable age at onset, caused by a heterozygous mutation in CRX.
A 43-year-old female with bull's eye maculopathy, whose sister was diagnosed with Stargardt disease previously at another centre, was found to have a single ABCA4 variant. Further examination of the family revealed that the asymptomatic father was also affected, indicating a dominant pattern of inheritance. In addition, the ABCA4 variant was not identified in the sister originally diagnosed with Stargardt disease. Next generation sequencing identified a heterozygous c.121C > T, p.R41W missense mutation in CRX in all 3 affected members.
We describe a common phenotype, but with variable age at onset, with autosomal dominant inheritance and reduced penetrance in a family found to have a pathogenic sequence variant in CRX. This illustrates the importance of panel based molecular genetic testing accompanied by family studies to establish a definitive diagnosis.
我们报告了一个患有黄斑营养不良的家族中的3名成员，最初被诊断为斯塔加特病，发病年龄差异显著，由CRX基因杂合突变引起。
一名患有靶心状黄斑病变的43岁女性，其姐姐此前在另一家中心被诊断为斯塔加特病，该女性被发现有一个单一的ABCA4变异。对该家族的进一步检查发现，无症状的父亲也受到影响，表明为显性遗传模式。此外，最初被诊断为斯塔加特病的姐姐未检测到ABCA4变异。下一代测序在所有3名受影响成员中均鉴定出CRX基因杂合的c.121C＞T、p.R41W错义突变。
我们描述了一种常见的表型，但发病年龄可变，具有常染色体显性遗传且外显率降低，该家族被发现有CRX基因的致病序列变异。这说明了基于基因panel的分子遗传学检测以及家族研究对于确立明确诊断的重要性。
