Abstract
IntroductionMutations in the teneurin transmembrane protein 4 (TENM4) gene, known to be involved in neuropsychiatric disorders, have been identified in three pedigree of essential tremor (ET) from Spain. ET has overlapping clinical manifestations and epidemiological symptoms with Parkinson’s disease (PD), suggesting these two disorders may reflect common genetic risk factors. In this study, we investigated clinical and genetic manifestations in four unrelated pedigrees with both ET and PD in which TENM4 variants were identified.MethodsWe subsequently explored whether TENM4 variants contributed to the risk of developing PD. The frequency of TENM4 variants was evaluated from four PD pedigrees and other 407 subjects.ResultsThe results revealed 12 different novel heterozygous variants, all at low frequency. A clear general enrichment of TENM4 variants was detected in early onset PD patients (p < 0.001, OR = 5.264, 95% CI = 1.957–14.158).ConclusionThe results indicate that rare TENM4 variants may be associated with an increased risk of PD.
Highlights
Mutations in the teneurin transmembrane protein 4 (TENM4) gene, known to be involved in neuropsychiatric disorders, have been identified in three pedigree of essential tremor (ET) from Spain
We subsequently explored whether TENM4 variants contributed to the risk of developing Parkinson’s disease (PD)
A clear general enrichment of TENM4 variants was detected in early onset PD patients (p < 0.001, odds ratio (OR) = 5.264, 95% confidence intervals (CI) = 1.957–14.158)
Summary
Mutations in the teneurin transmembrane protein 4 (TENM4) gene, known to be involved in neuropsychiatric disorders, have been identified in three pedigree of essential tremor (ET) from Spain. ET has overlapping clinical manifestations and epidemiological symptoms with Parkinson’s disease (PD), suggesting these two disorders may reflect common genetic risk factors. We investigated clinical and genetic manifestations in four unrelated pedigrees with both ET and PD in which TENM4 variants were identified. Parkinson’s disease (PD), one of the most frequent neurodegenerative disorders, is mainly characterized by bradykinesia, resting tremor and rigidity (Lees et al, 2009). 27 Mendelian genes have been reported to be linked with PD, and genome-wide association studies have succeeded in identifying many low-risk variants (Deng et al, 2018; Lunati et al, 2018). ET and PD are generally considered distinct entities, Spanaki and Plaitakis (2009) found ET occurred more frequently in relatives of PD patients, compared with
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