A 44-year-old Caucasian man presented with seizures and cognitive impairment. He had marked retinal drusen, and MR brain scan showed features of cerebral small vessel disease; he was diagnosed with a leukoencephalopathy of uncertain cause. He died at the age of 46 years and postmortem brain examination showed widespread small vessel changes described as a vasculopathy of unknown cause. Seven years postmortem, whole-genome sequencing identified a homozygous nonsense HTRA1 mutation (p.Arg302Ter), giving a retrospective diagnosis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy.
Data availability statement
Additional data on extensive investigations carried out on this patient prior to arrival at a diagnosis can be made available on request.
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Contributors RYYT coordinated the study, collected patient information and drafted the manuscript. AMD collected patient information and drafted the manuscript. KU prepared histopathological images and provided input on histopathological findings. CB prepared retinal photographs and provided input on ophthalmological findings. SG performed variant filtration and provided input on genetic analysis. HM was principal investigator of the Cerebral Small Vessel Disease arm of the BioResource Rare Disease Study. NJG was lead investigator on this case report, recruited the patient’s family, coordinated multidisciplinary authorship and drafted the manuscript.
Funding HM was supported by an NIHR Senior Investigator award. The work was supported by infrastructural support from the Cambridge Universities NIHR Biomedical Research Centre. RYYT was supported by the Agency for Science Technology and Research Singapore.
Disclaimer The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Competing interests None declared.
Provenance and peer review Not commissioned. Externally peer reviewed by Mike O’Sullivan, Queensland, Australia.
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