Targeted next generation sequencing and family survey enable correct genetic diagnosis in CRX associated macular dystrophy – a case report

BMC Ophthalmology

Suzanne Broadgate¹  Karl A. Z. Hudspith¹  Stephanie Halford¹  Andrea H. Németh²  Susan M. Downes³  Saoud Al-Khuzaei³  Morag E. Shanks⁴  Penny Clouston⁴ 

[1] Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK;Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK;Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK;Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK;Oxford Eye Hospital, John Radcliffe Hospital, Headley Way, OX9 3DU, Oxford, UK;Oxford Medical Genetics Laboratory, Oxford University Hospitals NHS Foundation Trust, Oxford, UK;

关键词: Retina;    Macular dystrophy;    Next generation sequencing;    CRX;    ABCA4 sequence variant, mutation;    Phenotype/genotype, reduced penetrance, family survey;   

DOI  :  10.1186/s12886-021-01919-1

来源: Springer

【 摘 要 】

BackgroundWe 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.Case presentationA 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.ConclusionsWe 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.

【 授权许可】

CC BY