The complex behavioral phenotype of 15q13.3 microdeletion syndrome

Abstract

The 15q13.3 deletion syndrome encompasses a heterogeneous behavioral phenotype that poses a major challenge to parents, caregivers, and treating providers. Further work to more clearly delineate genotype-phenotype relationships in 15q13.3 deletions will be important for anticipatory guidance and development of targeted therapies.Genet Med 18 11, 1111-1118.

The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications

“…Furthermore, an additional 30% (n=5) met the criteria for the ADOS-2 or ADI-R, but not both, indicating that autistic behaviors are prevalent in this group of patients. Based on this study, the prevalence of ASD among CHRNA7 duplication probands is higher than in most other genetic syndromes, such as 1q21.1 distal deletions (10%), 16p11.2 proximal deletions (27%), and even CHRNA7 deletions (31%), but is lower than some genetic syndromes, such as 1q21.1 duplications (41%) (Bernier et al, 2015; Hanson et al, 2010; Ziats et al, 2016). This emphasizes the need for parents of children with CHRNA7 duplications to be aware of potential autistic behaviors.…”

“…To further delineate the dosage sensitivity of CHRNA7 , we compared our duplication cohort to a recently published 15q13.3 deletion cohort (Ziats et al, 2016), assessed by the same team of investigators. Intellectual disability was present in both cohorts, with duplication probands’ DAS-II FSRIQ (p=0.0175) and NVRIQ (p=0.0088) measurements being significantly higher than deletion probands’ scores (Fig.…”

“…Genotypes of all probands were confirmed using genomic DNA isolated from blood samples subjected to multiplex ligation-dependent probe amplification (MLPA) as described previously (Ziats et al, 2016). Parents of each patient who were available and willing to participate were also tested with MLPA to determine CHRNA7 copy number and the inheritance pattern.…”

“…Patient characteristics, IQ measures, and behavioral scales were summarized using frequency with percentage, mean with standard deviation, and median with 25th and 75th percentiles. After testing for normality and outliers, a one-sample t-test was used to compare the sample mean to the mean of the normative score as well as to a previously assessed cohort of 15q13.13 deletion probands who were assessed by the same providers at Texas Children’s Hospital (Ziats et al, 2016). …”

An acetylcholine alpha7 positive allosteric modulator rescues a schizophrenia-associated brain endophenotype in the 15q13.3 microdeletion, encompassing CHRNA7

“…Cognitive deficits are also prevalent: 15q13.3 deletion carriers have an average nonverbal IQ of 60, show behavior abnormalities such as attention problems, hyperactivity and impairments in functional communication (Ziats et al, 2016).…”