ClinVar

Description

This deletion encompasses the recurrent deletion interval (15q13.3 recurrent region (BP4-BP5) including CHRNA7) associated with chromosome 15q13.3 deletion syndrome (OMIM 612001). The syndrome is associated with a broad range of clinical features including developmental delay, intellectual disability, autism spectrum disorder, facial dysmorphism, seizures, and neuropsychiatric and neurological disease. Collective penetrance of one or more of these features is high and may approach 80%. A recent report suggests this microdeletion syndrome has a prevalence of 1/5525, which is higher than previously estimated (Gillentine et al., J Hum Genet. 2018 Jul;63(7):795-801., PMID: 29691480). The majority of the deletions are inherited, most often maternally (Lowther et al., Genet Med. 2015 Feb;17(2):149-57. PMID: 25077648; Sharp, et. al, Nat Genet. 2008 Mar;40(3):322-8. PMID: 18278044; Hassfurther et al., Mol Syndromol. 2016 Feb;6(5):222-8. PMID: 26997942). Of note: the specific critical genes for every aspect of the 15q13.3 microdeletion phenotype are still under investigation, although CHRNA7 appears to be a top candidate gene for the neuropsychiatric manifestations (Gillentine et al., Biochem Pharmacol. 2015 Oct 15;97(4):352-62.PMID: 26095975; Hoppman-Chaney et al., Clin Genet. 2013 Apr;83(4):345-51., PMID: 22775350). Inheritance from a normal or mildly affected parent has been reported, suggesting incomplete penetrance and variable expressivity. See GeneReviews for additional information and references: www.ncbi.nlm.nih.gov/books/NBK50780/. Please expect the results of any other concurrent study in a separate report.