ArticleMolecular genetics & genomic medicine2019
Atypical nested 22q11.2 duplications between LCR22B and LCR22D are associated with neurodevelopmental phenotypes including autism spectrum disorder with incomplete penetrance.
Article in Molecular genetics & genomic medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Pooled it
- Chromosome 22q11.2 Microduplication Syndrome: A Review of the Literature and 12 New Cases.Genes · 2026Review
- The human intelligence evolved from proximalQuantitative biology (Beijing, China) · 2025Article
- Review
- Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus.Open biology · 2024Article
- Untargeted metabolomic, and proteomic analysis identifies metabolic biomarkers and pathway alterations in individuals with 22q11.2 deletion syndrome.Metabolomics : Official journal of the Metabolomic Society · 2024Article
- A Systematic Investigation of Complement and Coagulation-Related Protein in Autism Spectrum Disorder Using Multiple Reaction Monitoring Technology.Neuroscience bulletin · 2023Article
- Preliminary study of noninvasive prenatal screening for 22q11.2 deletion/duplication syndrome using multiplex dPCR assay.Orphanet journal of rare diseases · 2023Article
- High-Throughput Microscopy Analysis of Mitochondrial Membrane Potential in 2D and 3D Models.Cells · 2023Article
- Article
- Compound heterozygosity of a de novo submicroscopic deletion and an inherited frameshift pathogenic variant in theClinical case reports · 2023Article
- A Diagnosis of Maternal 22q Duplication and Mosaic Deletion following Prenatal Cell-Free DNA Screening.Case reports in genetics · 2023Article
- Diagnosis of prenatal 22q11.2 duplication syndrome: a two-case study.Journal of genetics · 2023Article
- Article
- Parent-Reported Social-Communicative Skills of Children with 22q11.2 Copy Number Variants and Siblings.Genes · 2022Article
- Cross-sectional and longitudinal findings in patients with proximal 22q11.2 duplication: A retrospective chart study.American journal of medical genetics. Part A · 2022Article
- A synonymous mutation inFrontiers in immunology · 2022Article
- PeakCNV: A multi-feature ranking algorithm-based tool for genome-wide copy number variation-association study.Computational and structural biotechnology journal · 2022Article
- Multiple Recurrent Copy Number Variations (CNVs) in Chromosome 22 Including 22q11.2 Associated with Autism Spectrum Disorder.Pharmacogenomics and personalized medicine · 2022Article
- Identifying of 22q11.2 variations in Chinese patients with development delay.BMC medical genomics · 2021Article
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Authors and funding
22 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChromosome 22q11.2 is susceptible to genomic rearrangements and the most frequently reported involve deletions and duplications between low copy repeats LCR22A to LCR22D. Atypical nested deletions and duplications are rarer and can provide a valuable opportunity to investigate the dosage effects of a smaller subset of genes within the 22q11.2 genomic disorder region.
methodsWe describe thirteen individuals from six families, each with atypical nested duplications within the central 22q11.2 region between LCR22B and LCR22D. We then compared the molecular and clinical data for patients from this study and the few reported atypical duplication cases, to the cases with larger typical duplications between LCR22A and LCR22D. Further, we analyzed genes with the nested region to identify candidates highly enriched in human brain tissues.
resultsWe observed that atypical nested duplications are heterogeneous in size, often familial, and associated with incomplete penetrance and highly variable clinical expressivity. We found that the nested atypical duplications are a possible risk factor for neurodevelopmental phenotypes, particularly for autism spectrum disorder (ASD), speech and language delay, and behavioral abnormalities. In addition, we analyzed genes within the nested region between LCR22B and LCR22D to identify nine genes (ZNF74, KLHL22, MED15, PI4KA, SERPIND1, CRKL, AIFM3, SLC7A4, and BCRP2) with enriched expression in the nervous system, each with unique spatiotemporal patterns in fetal and adult brain tissues. Interestingly, PI4KA is prominently expressed in the brain, and this gene is included either partially or completely in all of our subjects.
conclusionOur findings confirm variable expressivity and incomplete penetrance for atypical nested 22q11.2 duplications and identify genes such as PI4KA to be directly relevant to brain development and disorder. We conclude that further work is needed to elucidate the basis of variable neurodevelopmental phenotypes and to exclude the presence of a second disorder. Our findings contribute to the genotype-phenotype data for atypical nested 22q11.2 duplications, with implications for genetic counseling.
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