RNF213 vasculopathy manifested in various forms within a family: A case report

The ring finger protein 213 (RNF213) p.R4810K variant has been identified as being associated with Moyamoya disease (MMD), a condition that is more prevalent in East Asians. This association extends beyond cerebral vessels and has been implicated in coronary artery disease.

A 36-year-old female was admitted to the emergency room with chest pain. Although the patient had no known underlying conditions or risk factors for atherosclerosis, she was diagnosed with unstable angina and underwent percutaneous coronary intervention. Given her older sister's ongoing treatment for MMD, it was suspected that the patient's coronary artery disease might be linked to the MMD-associated gene mutation.

Coronary angiography revealed 80% narrowing of the proximal left anterior descending artery. Based on clinical symptoms and coronary angiography, we diagnosed it as unstable angina.

Due to the family history of MMD and detection of the RNF213 p.R4810K heterozygous variant in the patient's older sister, genetic counseling was recommended. Next-generation sequencing for vascular diseases was performed.

Genetic testing confirmed the presence of an RNF213 p.R4810K heterozygous variant in the patient, mirroring that in her sister. An RNF213 p.C4397R heterozygous variant was identified concomitantly, although it was categorized as a variant of uncertain significance. Coronary artery disease has been attributed to the RNF213 p.R4810K variant.

Although MMD is rare in Western populations, it is more common in East Asian populations. Traditionally, MMD diagnoses have focused solely on the cerebral vessels without guidelines for the assessment of other vascular involvements. This familial case underscores the fact that a single genetic mutation can manifest in diverse ways in different diseases. Hence, the need and regularity of systemic vessel screening should be thoughtfully considered in such a context.