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UK/FLY/2023/2543 v2

November 2023

SMS

Smith-Magenis Syndrome Overview
Flynn works with leading experts in the field to explore key issues in Smith–Magenis Syndrome (SMS), whilst offering practical tips and training that are applicable for use in the real world.

First described by Smith et al., SMS is a complex neurobehavioural disorder caused by either a 17p11.2 deletion, encompassing the retinoic acid-induced 1 (RAI1) gene, or a mutation of RAI1.

Approximately 90% of SMS cases have a 17p11.2 microdeletion, while the remaining 10% have a mutation in RAI1. Most SMS features are due to RAI1 haploinsufficiency, while the variability and severity of the disorder are modified by other genes in the 17p11.2 region.1

Investigation into the role that RAI1 plays in the regulation of gene transcription and circadian maintenance revealed that RAI1 regulates the transcription of circadian locomotor output cycles kaput (CLOCK), a key component of the mammalian circadian oscillator that transcriptionally regulates many critical circadian genes.2

References:

1. Elsea, S.H. and Girirajan, S. 2008, ‘Smith-Magenis Syndrome’, European Journal of Human Genetics. Volume 16, 412 – 421

2. Williams, S.R. et. al. 2012. ‘Smith-Magenis Syndrome Results in Disruption of CLOCK Gene Transcription and Reveals an Inegral Role for RAI1 in the Maintenance of Circadian Rhythmicity’, The American Journal of Human Genetics. Volume 90, Issue 6, 941-949