English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder characterized by multiple congenital anomalies. The syndrome is primarily ascribed to a ∼3.7 Mb  de novo  deletion on chromosome 17p11.2. Haploinsufficiency of multiple genes likely underlies the complex clinical phenotype.  RAI1  ( Retinoic Acid Induced 1 ) is recognized as a major gene involved in the SMS phenotype. Extensive genetic and clinical analyses of 36 patients with SMS-like features, but without the 17p11.2 microdeletion, yielded 10 patients with  RAI1  variants, including 4 with  de novo  deleterious mutations, and 6 with novel missense variants, 5 of which were  familial . Haplotype analysis showed two major  RAI1  haplotypes in our primarily Caucasian cohort; the novel  RAI1  variants did not occur in a preferred haplotype. RNA analysis revealed that  RAI1  mRNA expression was significantly decreased in cells of patients with the common 17p11.2 deletion, as well as in those with  de novo RAI1  variants. Expression levels varied in patients with familial  RAI1  variants and in non-17p11.2 deleted patients without identified  RAI1  defects. No correlation between SNP haplotype and  RAI1  expression was found. Two clinical features, ocular abnormalities and polyembolokoilomania (object insertion), were significantly correlated with decreased  RAI1  expression. While not significantly correlated, the presence of hearing loss, seizures, hoarse voice, childhood onset of obesity and specific behavioral aspects and the absence of immunologic abnormalities and cardiovascular or renal structural anomalies, appeared to be specific for the  de novo RAI1  subgroup. Recognition of the combination of these features will assist in referral for  RAI1  analysis of patients with SMS-like features without detectable microdeletion of 17p11.2. Moreover,  RAI1  expression emerged as a genetic target for development of therapeutic interventions for SMS.

Molecular Analysis of the Retinoic Acid Induced 1 Gene (RAI1) in Patients with Suspected Smith-Magenis Syndrome without the 17p11.2 Deletion