PER2 and sleep disorder: Moreover, similarly to SMS, MAND patients show sleep disorders and, in patient-derived lymphoblastoid cell lines, MBD5 haploinsufficiency was demonstrated to lead to the downregulation of clock circadian genes (CCG) (PER1, PER2, PER3, NR1D2, CRY2) and RAI1, thus linking circadian rhythm disruption to RAI1 expression [114].