Novel biallelic variants in NRROS associated with a lethal microgliopathy, brain calcifications, and neurodegeneration.
Negative regulator of reactive oxygen species (NRROS) is a leucine-rich repeat protein expressed by microglia and perivascular macrophages. To date, 9 individuals have been reported with biallelic NRROS variants. Here, we report one individual with a severe neurodegenerative phenotype in which exome sequencing identified 2 novel variants in NRROS, a missense variant (c.185T>C, p.Leu62Pro) and a premature stop codon (c.310C>T, p.Gln104Ter). Pathological examination revealed both extensive grey and white matter involvement, dystrophic calcifications, and infiltration of foamy macrophages. This is the first reported case of NRROS variants with a mitochondrial ultrastructure abnormality noted on electron microscopy analysis of post-mortem tissue.
Exome sequencing; Intracranial calcifications; NRROS; Pediatric neurodegeneration
Macintosh J, Derksen A, Poulin C, et al. Novel biallelic variants in NRROS associated with a lethal microgliopathy, brain calcifications, and neurodegeneration. Neurogenetics. 2022;23(2):151-156. doi:10.1007/s10048-022-00683-8