Significance of RNF213 in Clinical Management in China

Abstract

RNF213 is a main susceptibility gene for moyamoya disease. Worldwide, many mutations of RNF213 have been reported in association with moyamoya dis- ease. Among these, p.R4810K is the most frequent variant and is found in approxi- mately 95% of patients with familial moyamoya disease and in approximately 80% of sporadic cases in Japan. The variant is strongly associated with moyamoya dis- ease, with an odds ratio of nearly 200, but caution is necessary when it is used in clinical practice because there are approximately 2% of p.R4810K carriers who do not develop moyamoya disease in the general population. The clinical impact of the p.R4810K variant has been assessed by recent studies. Patients who are homozy- gous for the p.R4810K variant had an earlier onset age (mostly under the age of 4 years), and there was wider distribution (involvement of bilateral hemispheres and posterior circulation) and a more severe form of the disease with this variant. A contribution of RNF213 to various types of intracranial steno-occlusive disease including unilateral moyamoya disease, quasi-moyamoya disease, and other intra- cranial steno-occlusive disease was also reported. In this chapter, we will summa- rize genetic characteristics of moyamoya disease including familial cases and discuss clinical application of RNF213 genotyping in patients with moyamoya dis- ease and other intracranial steno-occlusive diseases.