15q13.3 Microdeletion Syndrome
15q13.3 microdeletion syndrome (OMIM 612001, DECIPHER coordinates: chr15: 30,901,306-32,445,407, hg19) is the result of heterozygous deletions at chromosome 15q13.3, ranging in size from ∼350 kb to 3.9 Mb. These deletions are mediated by nonallelic homologous recombination (NAHR) between four low copy repeat (LCR) elements: breakpoints (BPs) 3, 4, and 5, as well as the D-CHRNA7-LCR. The most common of these deletions, spanning 1.5 Mb to 2 Mb are mediated by BPs 4 and 5 and encompass six genes: FAN1, MTMR10, TRPM1, KLF13, OTUD7A, and CHRNA7, as well as one microRNA: hsa-miR-211. Of these genes, CHRNA7 and OTUD7A are the top candidate genes (Yin et al. 2018; Gillentine and Schaaf 2015).
The estimated frequency of the most common 15q13.3 microdeletions is 1 in 5525 live births (0.19%) and is estimated to be higher (0.29%) among individuals with intellectual disability and idiopathic generalized epilepsy (1%) (Gillentine et al. 2018). However, these...
References and Reading
- Gillentine, M. A., Schaaf, C. P. (2015). The human clinical phenotypes of altered CHRNA7 copy number. Biochem. Pharmaacol, 97(4), 352–362. https://doi.org/10.1016/j.bcp.2015.06.012
- Gillentine, M. A., Schaaf, C. P., & Patel, A. (2017). The importance of phase analysis in multiexon copy number variation detected by aCGH in autosomal recessive disorder loci. American Journal of Medical Genetics. Part A, 173, 2485–2488. https://doi.org/10.1002/ajmg.a.38328.CrossRefPubMedPubMedCentralGoogle Scholar
- Olincy, A., Blakeley-Smith, A., Johnson, L., et al. (2016). Brief report: Initial trial of Alpha7-nicotinic receptor stimulation in two adult patients with autism spectrum disorder. Journal of Autism and Developmental Disorders, 46, 3812–3817. https://doi.org/10.1007/s10803-016-2890-6.CrossRefPubMedGoogle Scholar