RT Journal Article
SR Electronic
T1 Filamin A Variant as a Possible Second-Hit Gene Promoting Moyamoya Disease–like Vascular Formation Associated With <em>RNF213</em> p.R4810K Variant
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams &amp; Wilkins
SP e200017
DO 10.1212/NXG.0000000000200017
VO 8
IS 5
A1 Yasuhito Ikeuchi
A1 Jiro Kitayama
A1 Noriyuki Sahara
A1 Takuya Okata
A1 Noriko Miyake
A1 Naomichi Matsumoto
A1 Takanari Kitazono
A1 Tetsuro Ago
YR 2022
UL http://ng.neurology.org/content/8/5/e200017.abstract
AB Background and Objective The objective of this case report was to identify a second-hit gene that may promote Moyamoya disease (MMD)–like vascular formation in an individual having the RNF213 p.R4810K variant.Methods We performed magnetic resonance imaging and genetic analyses of RNF213 and FLNA in a 21-year-old woman, who showed Ehlers-Danlos–like symptoms and developed a first-ever unprovoked seizure, and of her healthy parents.Results We identified bilateral periventricular nodular heterotopia (PNH) as the cause of seizures and MMD-like vascular formation in the patient. The patient had the RNF213 p.R4810K variant. Exome analysis identified c.4868delG in the X-linked FLNA gene encoding filamin A p.G1623V fs*41, which could explain PNH and Ehlers-Danlos–like symptoms. Her mother had the same FLNA variant and had asymptomatic bilateral PNH, whereas her father had the RNF213 variant and had normal cerebrovascular structure.Discussion The family study suggested that the FLNA variant promoted MMD-like vascular formation in a patient having the RNF213 variant, while the RNF213 variant amplified the phenotypic changes elicited by the FLNA abnormality. Collectively, we identified a gene abnormality in filamin A, a target of RNF213-mediated proteasomal degradation, that may promote MMD-like vascular formation as a possible second-hit gene in individuals having the RNF213 p.R4810K variant.