Available online 29 January 2023
Author links open overlay panel, , , , , , , , , , ABSTRACTRecently, a novel pathogenic variant in Annexin A1 protein (c.4G > A, p.Ala2Thr) has been identified in an Iranian consanguineous family with autosomal recessive parkinsonism. The deficiencies of ANXA1 could lead to extracellular SNCA accumulation, defects in intracellular signaling pathways and synaptic plasticity causing parkinsonism. The aim of this study was to identify rare ANXA1 variants in 95 early-onset PD patients from South Italy. Sequencing analysis of ANXA1 gene revealed only 2 synonymous variants in PD patients (rs1050305, rs149033255). Therefore, we conclude that the recently published ANXA1 mutation is not a common cause of EOPD in Southern Italy.
Section snippetsINTRODUCTIONParkinson's disease affects 1-2% of the population above the age of 60 years old. Less than 10% of people with the disease are younger than 45 years of age at the moment of the onset of symptoms (Mehanna and Jankovic, 2019). The classification of Parkinson's disease was revolutionized by sequencing technologies (Shulskaya et al., 2018). Recently, indeed, linkage analysis and exome sequencing increased the number of genes involved in monogenic forms of PD. A mutation in the ANXA1 gene was
MATERIALS AND METHODSSequencing analysis of ANXA1 was performed to evaluate the presence of mutations in a Southern Italy cohort of 95 early onset PD (51% women; mean age at onset, 40.2 ± 9.4 years), clinically diagnosed by neurologists according to the UK Brain Bank criteria (Hughes et al.,1992). The Institute of Neurology, Department of Medical Sciences, University of Magna Graecia (Cz) recruited all patients who signed an informed consent. Finally, the study was approved by the local ethics committee. Genomic
RESULTSNo rare protein-coding variant was detected in ANXA1 gene in our PD cohort of 95 patients. Sanger sequencing detected only two synonymous variants: p.Leu109= (c.327A>G, rs1050305) and p.Arg212= (c.636G>A, rs149033255). The rs1050305 was identified in fifteen PD patients in heterozygous form and one in homozygous form, while the rs149033255 was observed in only one PD patient in heterozygosity. Both variants were reported in GnomAD with MAF G=0.107972 and A=0.002226, respectively. The in-silico
DISCUSSIONA combination of homozygosity mapping and Whole Genome sequencing strategies lead to identification of a new gene, ANXA1, involved in parkinsonism. ANXA1 is located on chromosome 9q21.13 and it consists of 13 exons (NM_000700.3). This gene encodes a binding-phospholipids protein (annexin A1), that inhibits phospholipase A2 and has anti-inflammatory activity. Previously, annexin A1 was associated with neurodegenerative disorders, including multiple sclerosis and Alzheimer's disease (Ries et al.,
Uncited ReferencesRaja and Joseph, 2019 Aug
CRediT authorship contribution statementMonica Gagliardi: Conceptualization. Radha Procopio: . Mariagrazia Talarico: . Andrea Quattrone: . Gennarina Arabia: . Maurizio Morelli: . Marco D'Amelio: . Donatella Malanga: Investigation, Data curation, Formal analysis. Giuseppe Bonapace: Resources. Aldo Quattrone: Writing – review & editing. Grazia Annesi: Conceptualization.
ACKNOWLEDGMENTThe authors thank Lorenzo Gagliardi, PhD student in Method and Model for Economic Decisions, Department of Economics, University of Insubria, Italy.
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