Smith–Magenis Syndrome

Elsea, Sarah H.; Finucane, Brenda

doi:10.1002/9780470015902.a0021428

Cited by 21 publications

(39 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 The coarse facial appearance as well as the ID with variable behavior problems of the individuals with WAC mutations have similarities with individuals reported with Smith-Magenis syndrome. 35 Interstitial deletions including WAC were previously described and associated with ID. [14][15][16][17] Wentzel et al 14 presented six individuals with an interstitial deletion at 10p12p11, all sharing a region of overlap including two genes: BAMBI and WAC.…”

Section: Discussionmentioning

confidence: 99%

De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila

et al. 2016

View full text Add to dashboard Cite

Recently WAC was reported as a candidate gene for intellectual disability (ID) based on the identification of a de novo mutation in an individual with severe ID. WAC regulates transcription-coupled histone H2B ubiquitination and has previously been implicated in the 10p12p11 contiguous gene deletion syndrome. In this study, we report on 10 individuals with de novo WAC mutations which we identified through routine (diagnostic) exome sequencing and targeted resequencing of WAC in 2326 individuals with unexplained ID. All but one mutation was expected to lead to a loss-of-function of WAC. Clinical evaluation of all individuals revealed phenotypic overlap for mild ID, hypotonia, behavioral problems and distinctive facial dysmorphisms, including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin. These clinical features were also previously reported in individuals with 10p12p11 microdeletion syndrome. To investigate the role of WAC in ID, we studied the importance of the Drosophila WAC orthologue (CG8949) in habituation, a non-associative learning paradigm. Neuronal knockdown of Drosophila CG8949 resulted in impaired learning, suggesting that WAC is required in neurons for normal cognitive performance. In conclusion, we defined a clinically recognizable ID syndrome, caused by de novo loss-of-function mutations in WAC. Independent functional evidence in Drosophila further supported the role of WAC in ID. On the basis of our data WAC can be added to the list of ID genes with a role in transcription regulation through histone modification.

show abstract

Section: Discussionmentioning

confidence: 99%

De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila

et al. 2016

View full text Add to dashboard Cite

show abstract

“…1,2 Craniofacial features include brachycephaly, midface hypoplasia, tented upper lip, relative prognathism with age and deep-set and hypoteloric eyes. 3,4 Skeletal features include brachydactyly, short stature and short/ broad hands. 3,4 The behavioral phenotype includes onychotillomania, polyembolokoilamania, 'hand licking and page flipping' , 'self-hugging' and hyperactivity.…”

Section: Smith-magenis Syndrome (Sms Mim 182290mentioning

confidence: 99%

“…3,4 Skeletal features include brachydactyly, short stature and short/ broad hands. 3,4 The behavioral phenotype includes onychotillomania, polyembolokoilamania, 'hand licking and page flipping' , 'self-hugging' and hyperactivity. 5 Sleep disturbance is present in 88% of SMS patients and is characterized by difficulty getting to sleep, frequent nocturnal awakenings, early sleep offset and daytime sleepiness with a need for daytime naps.…”

Section: Smith-magenis Syndrome (Sms Mim 182290mentioning

confidence: 99%

“…3 The classical SMS deletions span B3.5 Mb of 17p11.2 and are present in B70% of affected individuals. 3,8,9 Atypical (smaller or larger) deletions, including the 17p11.2 band, occur in B20% of other affected individuals. 3,8,9 Mutations in the RAI1 gene have been observed in B10% of all reported SMS patients.…”

Section: Smith-magenis Syndrome (Sms Mim 182290mentioning

confidence: 99%

“…3 The classical SMS deletions span B3.5 Mb of 17p11.2 and are present in B70% of affected individuals.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Detection of classical 17p11.2 deletions, an atypical deletion and RAI1 alterations in patients with features suggestive of Smith–Magenis syndrome

et al. 2011

View full text Add to dashboard Cite

Smith-Magenis syndrome (SMS) is a complex disorder whose clinical features include mild to severe intellectual disability with speech delay, growth failure, brachycephaly, flat midface, short broad hands, and behavioral problems. SMS is typically caused by a large deletion on 17p11.2 that encompasses multiple genes including the retinoic acid induced 1, RAI1, gene or a mutation in the RAI1 gene. Here we have evaluated 30 patients with suspected SMS and identified SMS-associated classical 17p11.2 deletions in six patients, an atypical deletion of B139 kb that partially deletes the RAI1 gene in one patient, and RAI1 gene nonsynonymous alterations of unknown significance in two unrelated patients. The RAI1 mutant proteins showed no significant alterations in molecular weight, subcellular localization and transcriptional activity. Clinical features of patients with or without 17p11.2 deletions and mutations involving the RAI1 gene were compared to identify phenotypes that may be useful in diagnosing patients with SMS. European Journal of Human Genetics (2012) 20, 148-154; doi:10.1038/ejhg.2011.167; published online 7 September 2011Keywords: Smith-Magenis syndrome; 17p11.2; RAI1; arrayCGH; mutation; deletion INTRODUCTION Smith-Magenis syndrome (SMS, MIM 182290) is a multiple congenital anomalies and intellectual disability syndrome associated with a deletion of chromosome 17p11. 2. The incidence of SMS is estimated to be B1:15 000-1:25 000 births. 1 SMS is most commonly characterized by a variable degree of intellectual disability including speech and motor delay, craniofacial and skeletal anomalies, sleep disturbance, self-injurious and attention-seeking behaviors. 1,2 Craniofacial features include brachycephaly, midface hypoplasia, tented upper lip, relative prognathism with age and deep-set and hypoteloric eyes. 3,4 Skeletal features include brachydactyly, short stature and short/ broad hands. 3,4 The behavioral phenotype includes onychotillomania, polyembolokoilamania, 'hand licking and page flipping' , 'self-hugging' and hyperactivity. 5 Sleep disturbance is present in 88% of SMS patients and is characterized by difficulty getting to sleep, frequent nocturnal awakenings, early sleep offset and daytime sleepiness with a need for daytime naps. 6,7 SMS clinical features overlap with other intellectual disability syndromes such as Prader-Willi, Williams and Down's syndromes, which often complicate its clinical diagnosis.A majority, B90%, of SMS patients have a deletion of chromosome 17p11.2 that includes the RAI1 gene. 3 The classical SMS deletions span B3.5 Mb of 17p11.2 and are present in B70% of affected individuals.

show abstract

Duplication of the Rubinstein–Taybi region on 16p13.3 is associated with a distinctive phenotype

Marangi

Leuzzi

Orteschi

et al. 2008

American J of Med Genetics Pt A

View full text Add to dashboard Cite

We report on a 16-year-old girl with a multiple congenital anomalies/mental retardation condition, in which a 1.7 Mb tandem duplication of chromosome region 16p13.3 was detected by array-CGH. Mental retardation was moderate (IQ 45), with very limited speech. She had tall stature with relative microcephaly. Clinical manifestations included distinctive facial appearance with deep set eyes, narrow palpebral fissures, wide nasal bridge, long philtrum, rounded nasal tip, thin upper lip, protruding mandible and abnormal auricles, hand and foot anomalies. The causal 16p13.3 duplication is one of the smallest reported so far, and includes the CBP gene, whose haploinsufficiency is responsible for the Rubinstein-Taybi syndrome. By comparing clinical manifestations of our patient with those of patients carrying similar rearrangements, we could infer that 16p13.3 microduplications encompassing the Rubinstein-Taybi region result in a recognizable clinical condition, most likely representing a single gene disorder.

show abstract

Smith–Magenis Syndrome

Cited by 21 publications

References 35 publications

De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila

De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila

Detection of classical 17p11.2 deletions, an atypical deletion and RAI1 alterations in patients with features suggestive of Smith–Magenis syndrome

Duplication of the Rubinstein–Taybi region on 16p13.3 is associated with a distinctive phenotype

Contact Info

Product

Resources

About