Beyond IQ: executive function deficits and their relation to functional, clinical, and neuroimaging outcomes in 3q29 deletion syndrome.

Background: 3q29 deletion syndrome (3q29del) is a rare (~1:30 000) genomic disorder associated with a wide array of neurodevelopmental and psychiatric phenotypes. Prior work by our team identified clinically significant executive function (EF) deficits in 47% of individuals with 3q29del; however, the nuances of EF in this population have not been described.

Methods: We used the Behavior Rating Inventory of Executive Function (BRIEF) to perform the first in-depth assessment of real-world EF in a cohort of 32 individuals with 3q29del (62.

Scaled and efficient derivation of loss-of-function alleles in risk genes for neurodevelopmental and psychiatric disorders in human iPSCs.

Translating genetic findings for neurodevelopmental and psychiatric disorders (NPDs) into actionable disease biology would benefit from large-scale and unbiased functional studies of NPD genes. Leveraging the cytosine base editing (CBE) system, we developed a pipeline for clonal loss-of-function (LoF) allele mutagenesis in human induced pluripotent stem cells (hiPSCs) by introducing premature stop codons (iSTOP) that lead to mRNA nonsense-mediated decay (NMD) or protein truncation. We tested the pipeline for 23 NPD genes on 3 hiPSC lines and achieved highly reproducible, efficient iSTOP editing in 22 genes.

Scaled and Efficient Derivation of Loss of Function Alleles in Risk Genes for Neurodevelopmental and Psychiatric Disorders in Human iPSC.

Translating genetic findings for neurodevelopmental and psychiatric disorders (NPD) into actionable disease biology would benefit from large-scale and unbiased functional studies of NPD genes. Leveraging the cytosine base editing (CBE) system, here we developed a pipeline for clonal loss-of-function (LoF) allele mutagenesis in human induced pluripotent stem cells (hiPSCs) by introducing premature stop-codons (iSTOP) that lead to mRNA nonsense-mediated-decay (NMD) or protein truncation. We tested the pipeline for 23 NPD genes on 3 hiPSC lines and achieved highly reproducible, efficient iSTOP editing in 22 NPD genes.

Behavioral Phenotypes and Comorbidity in 3q29 Deletion Syndrome: Results from the 3q29 Registry.

3q29 deletion syndrome (3q29del) is associated with a significantly increased risk for neurodevelopmental and neuropsychiatric disorders. However, the full spectrum of behavioral phenotypes associated with 3q29del is still evolving. Individuals with 3q29del (n = 96, 60.

Musculoskeletal phenotypes in 3q29 deletion syndrome.

3q29 deletion syndrome (3q29del) is a rare genomic disorder caused by a 1.6 Mb deletion (hg19, chr3:195725000-197350000). 3q29del is associated with neurodevelopmental and psychiatric phenotypes, including an astonishing >40-fold increased risk for schizophrenia, but medical phenotypes are less well-described.

Acetate supplementation rescues social deficits and alters transcriptional regulation in prefrontal cortex of Shank3 deficient mice.

Background: The pathophysiology of autism spectrum disorder (ASD) involves genetic and environmental factors. Mounting evidence demonstrates a role for the gut microbiome in ASD, with signaling via short-chain fatty acids (SCFA) as one mechanism. Here, we utilize mice carrying deletion to exons 4-22 of Shank3 (Shank3) to model gene by microbiome interactions in ASD.

Visual-Motor Integration Deficits in 3q29 Deletion Syndrome.

3q29 deletion syndrome (3q29del) is associated with neuropsychiatric and neurodevelopmental phenotypes. We previously reported that graphomotor weakness is present in up to 78% of individuals with 3q29del. We have now explored nuances of the graphomotor phenotype and its association with other comorbidities in this population.

Musculoskeletal phenotypes in 3q29 deletion syndrome.

3q29 deletion syndrome (3q29del) is a rare genomic disorder caused by a 1.6 Mb deletion (hg19, chr3:195725000â€"197350000). 3q29del is associated with neurodevelopmental and psychiatric phenotypes, including an astonishing >40-fold increased risk for schizophrenia, but medical phenotypes are less well-described.

Adaptive behavior deficits in individuals with 3q29 deletion syndrome.

Background: 3q29 deletion syndrome (3q29del) is associated with a significantly increased risk for neurodevelopmental and neuropsychiatric phenotypes. Mild to moderate intellectual disability (ID) is common in this population, and previous work by our team identified substantial deficits in adaptive behavior. However, the full profile of adaptive function in 3q29del has not been described, nor has it been compared to other genomic syndromes associated with elevated risk for neurodevelopmental and neuropsychiatric phenotypes.

Autism spectrum disorder symptom expression in individuals with 3q29 deletion syndrome.

Background: The 1.6 Mb 3q29 deletion is associated with neurodevelopmental and neuropsychiatric phenotypes, including a 19-fold increased risk for autism spectrum disorder (ASD). Previous work by our team identified elevated social disability in this population via parent-report questionnaires.

Large 22q13.3 deletions perturb peripheral transcriptomic and metabolomic profiles in Phelan-McDermid syndrome.

Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused at least in part by haploinsufficiency of the SHANK3 gene, due to sequence variants in SHANK3 or subtelomeric 22q13.3 deletions. Phenotypic differences have been reported between PMS participants carrying small "class I" mutations and large "class II" mutations; however, the molecular perturbations underlying these divergent phenotypes remain obscure.

Metabolic effects of the schizophrenia-associated 3q29 deletion.

The 1.6 Mb 3q29 deletion is associated with developmental and psychiatric phenotypes, including a 40-fold increased risk for schizophrenia. Reduced birth weight and a high prevalence of feeding disorders in patients suggest underlying metabolic dysregulation.

Symptoms of Pediatric Feeding Disorders Among Individuals with 3q29 Deletion Syndrome: A Case-Control Study.

Objective: The goal of this study was to evaluate symptoms of pediatric feeding disorder in a sample of individuals with 3q29 deletion syndrome (3q29Del). Previous research has found that individuals with 3q29Del may experience elevated feeding concerns in early childhood; however, the specificity of these feeding concerns is not well understood.

Methods: We compared individuals with 3q29Del (N = 83) with controls (N = 59) using an 11-item survey that assessed commonly reported symptoms associated with pediatric feeding disorders.

New phenotypes associated with 3q29 duplication syndrome: Results from the 3q29 registry.

3q29 duplication syndrome (3q29dup) is a rare genomic disorder caused by a 1.6 Mb duplication (GRCh38 chr3:195,998,000-197,623,000). Case reports indicate the 3q29dup is likely to be pathogenic, but the full range of manifestations is not well understood.

Neuropsychiatric phenotypes and a distinct constellation of ASD features in 3q29 deletion syndrome: results from the 3q29 registry.

Background: The 1.6 Mb 3q29 deletion is associated with neurodevelopmental and psychiatric phenotypes, including increased risk for autism spectrum disorder (ASD) and a 20 to 40-fold increased risk for schizophrenia. However, the phenotypic spectrum of the deletion, particularly with respect to ASD, remains poorly described.

Behavioral changes and growth deficits in a CRISPR engineered mouse model of the schizophrenia-associated 3q29 deletion.

The 3q29 deletion confers increased risk for neuropsychiatric phenotypes including intellectual disability, autism spectrum disorder, generalized anxiety disorder, and a >40-fold increased risk for schizophrenia. To investigate consequences of the 3q29 deletion in an experimental system, we used CRISPR/Cas9 technology to introduce a heterozygous deletion into the syntenic interval on C57BL/6 mouse chromosome 16. mRNA abundance for 20 of the 21 genes in the interval was reduced by ~50%, while protein levels were reduced for only a subset of these, suggesting a compensatory mechanism.

The origin of exotic pet sugar gliders () kept in the United States of America.

The demand for exotic non-domesticated animals kept as pets in the United States of America (USA) is increasing the exportation rates of these species from their native ranges. Often, illegal harvesting of these species is used to boost captive-bred numbers and meet this demand. One such species, the sugar glider (), endemic to Australia and New Guinea is a popular domestic pet due to its small size and "cute" demeanour.