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Table 3 Examples of pleiotropy in neurological disorders and possible mechanisms

From: The role of gene variants in the pathogenesis of neurodegenerative disorders as revealed by next generation sequencing studies: a review

Diverse phenotype with Possible mechanisms Examples References
Different mutations in the same gene Different mutations may have different downstream effects VCP mutations are found in ALS, FTD and inclusion body myopathy. Nalbandian et al., 2011 [47]
Different variants confer different levels of pathogenicity SNCA point mutations are highly penetrant for PD while penetrance for dosage mutation is linked to copy number; common variants increase PD risk only slightly. Singleton et al., 2016 [36]
Same mutation in the same gene Presence of modifier gene TMEM106b minor allele is protective of FTD but not ALS in patients with C9orf72 repeat expansion. van Blitterswijk et al., 2014 [51]
Oligogenic inheritance FALS patients with SOD1 mutation and additional rare variants in ALS genes have reduced survival. Pang et al., 2017 [42]
Different effects in different cell lines TGM6 mutation found in families with SCA and a family with leukemia. Pan et al., 2014 [48]