While we note, however, that the use of EGFP fusion constructs may confound precise measurements of DNMT1 stability due to the long half-life of EGFP, our results are consistent with previous studies of clinical DNMT1 hotspot mutations found in hereditary sensory and autonomic neuropathy type 1E (HSAN1E) and autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) patients, demonstrating that mutations in the RFTS domain destabilize DNMT1 (Klein et al., 2011; Winkelmann et al., 2012; Smets et al., 2017). Here, DNMT1 is linked to hereditary sensory neuropathy-deafness-dementia syndrome.