Connexion

GENATLAS PHENOTYPE

last update : 20-06-2012

Symbol	SMS
Location	17p11.2
HGNC id	11113
Name	Smith-Magenis syndrome
Other name(s)	interstitial deletion of 17p11.2, monosomy 17p11.2
Corresponding gene	SMCR , RAI1
Other symbol(s)	DEL17P11, del(17)(p11.2p11.2)
Main clinical features	distinct cranio-facial features with midface retraction, short philtrum and everted upper lip mental retardation, sleep disturbance, self-injurious and agressive behavior multiple congenital anomalies obesity ophtalmological and otolaryngologic anomalies(>80%), hearing impairment(~70%), cardiac (~40%) and renal (~20-30%) defects
Genetic determination	chromosomal
	genomic disorder
Prevalence	estimated at 1/25000, probably higher due to under-diagnosis
Function/system disorder	mental retardation
	multisystem/generalized
Type	MCA/MR

Gene product

Name

contiguous gene syndrome, major gene : retinoic acid induced 1; RAI1 is a positive transcriptional regulator of CLOCK (PMID: 22578325)

Mechanism(s)

Chromosome rearrangement	Effect	Comments

deletion	haploinsufficiency	commonly deleted region of 3.5Mb between REPD and REPP in 75 percent of cases, atypical deletion from 1.5 to 9 Mb in others, minimum deletion of ~650kb including RAI1.
	haploinsufficiency	in rare patients, mutations in the RAI1 gene, with phenotypic variability

Remark(s)

RAI1 directly regulate circadian rhythms ( PMID: 22578325 )

Genotype/Phenotype correlations

general absence of short stature and lack of visceral anomalies distinguish patients with RAI1 mutations from patients with deletions ; patients with mutations are more likely to exhibit obesity and overgrowth phenotypes. Larger deletion may be associated with cleft palate; Rai1 haploinsufficiency represents a single-gene model of obesity with hyperphagia, abnormal fat distribution and altered hypothalamic gene expression associated with satiety, food intake, behavior and obesity (PMID: 20663924))