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

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.

SUBMITTER: Macintosh J

PROVIDER: S-EPMC9289721 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Macintosh Julia J Derksen Alexa A Poulin Chantal C Braverman Nancy N Vanderver Adeline A Thiffault Isabelle I Albrecht Steffen S Bernard Geneviève G

Neurogenetics 20220131 2

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 an ...[more]

PMID: 35099671

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