Novel biallelic variants in NRROS associated with a lethal microgliopathy, brain calcifications, and neurodegeneration.

Creator(s)

Julia Macintosh
Alexa Derksen
Chantal Poulin
Nancy Braverman
Adeline Vanderver
Isabelle Thiffault, Children's Mercy HospitalFollow
Steffen Albrecht
Geneviève Bernard

Document Type

Article

Publication Date

4-2022

Identifier

DOI: 10.1007/s10048-022-00683-8

Abstract

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.

Journal Title

Neurogenetics

Volume

23

Issue

2

First Page

151

Last Page

156

Keywords

Exome sequencing; Intracranial calcifications; NRROS; Pediatric neurodegeneration

Comments

Grant support

• U54 NS115052/NS/NINDS NIH HHS/United States

Recommended Citation

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