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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



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]