Toggle Main Menu Toggle Search

Open Access padlockePrints

Long-term follow-up of a patient with JAG1-associated retinopathy

Lookup NU author(s): Stephanie Quinn, Stephen Clark, Dr Richard Martin, Andrew Browning


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


© 2021, Crown.Purpose: To report the long-term structural and functional changes in the posterior segments of an adult with an unusual retinal dystrophy caused by a novel mutation in JAG1. Methods: A 33-year-old female underwent comprehensive ophthalmic examination, including best corrected visual acuity (BCVA) measurement, dilated fundus imaging (wide-angle fundus colour and short wavelength autofluorescence imaging), macular and peripheral spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG) at baseline and 10 years later at the age of 43. The patient also underwent systemic review with detailed cardiac, brain and renal investigations. During follow-up, genetic analysis using whole-exome sequencing was performed on the patient and her parents to identify disease-causing variants. Results: The patient’s main complaint was of a recent onset of bilateral photophobia and blurred vision in the left eye. On examination, the most striking retinal finding was of bilateral well-demarcated, anterior circumferential chorioretinal atrophy with scattered pigment clumping from the mid periphery to the ora. In addition, she had posterior pole RPE hypopigmentation, peripapillary chorioretinal atrophy, left macular choroidal folds and retinal vasculature tortuosity with atypical branching. Her retinal electrophysiology was consistent with a cone rod photoreceptor dystrophy and left macular dysfunction. Ten years later, her BCVA, the anterior circumferential chorioretinal atrophy and her visual field constriction all remained stable. Her retinal electrophysiology demonstrated deterioration of left rod function, while cone dysfunction remained stable. Macular function deteriorated in both eyes. During follow-up, she was also noted to have progressive aortic root dilatation, posterior embryotoxon and an x ray diagnosis of butterfly vertebrae. Whole-exome sequencing revealed a novel c.2412C > A p.(Tyr804Ter) truncating mutation in JAG1 that was predicted to be pathogenic and suggested a diagnosis of Alagille syndrome. Conclusion: This is the first report of the long-term detailed follow-up of a patient with Alagille syndrome whose most striking ophthalmic finding was bilateral well-demarcated, anterior circumferential chorioretinal atrophy. During follow-up, this finding remained stable, suggesting that this may be developmental in origin. This is in contrast with the progressive deterioration in the posterior pole retinal and macular function.

Publication metadata

Author(s): Cheema MR, Stone LG, Sellar PW, Quinn S, Clark SC, Martin RJ, O'Brien JM, Warriner C, Browning AC

Publication type: Article

Publication status: Published

Journal: Documenta Ophthalmologica

Year: 2021

Volume: 143

Pages: 237-247

Print publication date: 01/10/2021

Online publication date: 20/04/2021

Acceptance date: 02/04/2021

ISSN (print): 0012-4486

ISSN (electronic): 1573-2622

Publisher: Springer Science and Business Media Deutschland GmbH


DOI: 10.1007/s10633-021-09836-w

PubMed id: 33877487


Altmetrics provided by Altmetric