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ANXA1 with Anti‐Inflammatory Properties Might Contribute to Parkinsonism
Author(s) -
Darvish Hossein,
Azcona Luis J.,
Taghavi Shaghayegh,
Firouzabadi Saghar Ghasemi,
Tafakhori Abbas,
Alehabib Elham,
Mohajerani Fatemeh,
Zardadi Safoura,
PaisánRuiz Coro
Publication year - 2021
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.26148
Subject(s) - parkinsonism , zebrafish , microglia , neuroprotection , biology , genetics , disease , phagocytosis , snp , mutant , disease gene identification , neurotoxicity , mutation , neuroscience , gene , single nucleotide polymorphism , medicine , exome sequencing , immunology , inflammation , pathology , genotype , toxicity
We here describe the identification of a novel variant in the anti‐inflammatory Annexin A1 protein likely to be the cause of disease in two siblings with autosomal recessive parkinsonism. The disease‐segregating variant was ascertained through a combination of homozygosity mapping and whole genome sequencing and was shown to impair phagocytosis in zebrafish mutant embryos. The highly conserved variant, absent in healthy individuals and public SNP databases, affected a functional domain of the protein with neuroprotective properties. This study supports the hypothesis that damaged microglia might lead to impairments in the clearance of accumulated and aggregated proteins resulting in parkinsonism. ANN NEUROL 2021;90:319–323