与致死性小胶质病变、脑钙化和神经变性相关的新型NRROS双等位基因变异。

IF 1.6 4区医学 Q3 CLINICAL NEUROLOGY Neurogenetics Pub Date : 2022-04-01 DOI:10.1007/s10048-022-00683-8

Julia Macintosh, Alexa Derksen, Chantal Poulin, Nancy Braverman, Adeline Vanderver, Isabelle Thiffault, Steffen Albrecht, Geneviève Bernard

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引用次数: 2

摘要

活性氧负调节因子(NRROS)是一种富含亮氨酸的重复蛋白，由小胶质细胞和血管周围巨噬细胞表达。迄今为止，已有9人报告了双等位NRROS变异。在这里，我们报告了一个患有严重神经退行性表型的个体，其外显子组测序发现了NRROS的2个新变体，一个错义变体(C . 185t >C, p.Leu62Pro)和一个过早停止密码子(C . 310c >T, p.Gln104Ter)。病理检查显示广泛的灰质和白质受累，营养不良的钙化，泡沫性巨噬细胞浸润。这是首次报道的NRROS变异与死后组织电镜分析中发现的线粒体超微结构异常的病例。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.

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来源期刊

Neurogenetics 医学-临床神经学

CiteScore

3.90

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Neurogenetics publishes findings that contribute to a better understanding of the genetic basis of normal and abnormal function of the nervous system. Neurogenetic disorders are the main focus of the journal. Neurogenetics therefore includes findings in humans and other organisms that help understand neurological disease mechanisms and publishes papers from many different fields such as biophysics, cell biology, human genetics, neuroanatomy, neurochemistry, neurology, neuropathology, neurosurgery and psychiatry. All papers submitted to Neurogenetics should be of sufficient immediate importance to justify urgent publication. They should present new scientific results. Data merely confirming previously published findings are not acceptable.