15q11.2 proximal imbalances associated with a diverse array of neuropsychiatric disorders and mild dysmorphic features
Abstract
Deletion within the proximal region of chromosome 15q11.2 between breakpoints 1 and 2 (BP1-BP2) has been proposed to be a risk factor for intellectual disability, seizure, and schizophrenia. However, the clinical significance of its reciprocal duplication is not clearly defined yet. We evaluated 1654 consecutive pediatric patients with various neurological disorders by high-resolution microarray-based comparative genomic hybridization. We identified 21 patients carrying 15q11.2 BP1-BP2 deletion and 12 patients carrying 15q11.2 BP1-BP2 duplication in this cohort, which represent 1.27% (21/1,654) and 0.7% (12/1,654) of the patients analyzed, respectively. Approximately 87.5% of the patients carrying the deletion and 80% of the patients carrying the duplication have developmental delay or intellectual disability. Other recurrent clinical features in these patients include mild dysmorphic features, autistic spectrum disorders, and epilepsy. Our observations provide further evidence in favor of a strong association of 15q11.2 BP1-BP2 deletion with a variety of neuropsychiatric disorders. The diversity of clinical findings in these patients expands the phe-notypic spectrum of individuals carrying the deletion. In addition, possible etiological effects of 15q11.2 BP1-BP2 duplication in neuropsychiatric disorders are proposed.
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10/29 (35%) of individuals with the 15q11.2 BP1-BP2 microdeletion inherited their deletion from an abnormal parent.
“The review of literature from six published reports summarized by Cafferkey et al. [18] regarding information on the inheritance of the 15q11.2 BP1–BP2 microdeletion indicates that 22/43 (51%) of individuals with the microdeletion, where parental data were available, inherited their deletion from an apparently healthy parent while 10/29 (35%) of individuals inherited their deletion from an abnorma”
From The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review (2015) · cites this paper as [17]
Abdelmoity et al. found that 21% or 1.27% of 1654 consecutive pediatric patients with neurological disorders carried a 15q11.2 BP1-BP2 deletion.
“Later, Abdelmoity et al. [17] reported a cohort of 1654 consecutive pediatric patients presenting with a range of neurological disorders and found that 21% or 1.27% of the patients carried a 15q11.2 BP1–BP2 deletion.”
From The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review (2015) · cites this paper as [17]
22/43 (51%) of individuals with the 15q11.2 BP1-BP2 microdeletion, where parental data were available, inherited their deletion from an apparently healthy parent.
“The review of literature from six published reports summarized by Cafferkey et al. [18] regarding information on the inheritance of the 15q11.2 BP1–BP2 microdeletion indicates that 22/43 (51%) of individuals with the microdeletion, where parental data were available, inherited their deletion from an apparently healthy parent while 10/29 (35%) of individuals inherited their deletion from an abnorma”
From The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review (2015) · cites this paper as [17]
87.5% of patients with the 15q11.2 BP1-BP2 deletion in Abdelmoity et al. had developmental delay or intellectual disability.
“They found that 87.5% of the patients with the deletion had developmental delay or intellectual disability.”
From The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review (2015) · cites this paper as [17]
Cites
Large recurrent microdeletions associated with schizophrenia.
GROUP, Stefansson, H., Rujescu, D., Cichon, S., Pietiläinen, O. P. H., Ingason, A., Steinberg, S., Fossdal, R., Sigurdsson, E., Sigmundsson, T., et al. (2008) · Nature · doi:10.1038/nature07229 · Cited by 1,745 · see citing works
Common variants conferring risk of schizophrenia
†Genetic Risk and Outcome in Psychosis (GROUP), Stefansson, H., Ophoff, R. A., Steinberg, S., Andreassen, O. A., Cichon, S., Rujescu, D., Werge, T., Pietiläinen, O. P. H., Mors, O., et al. (2009) · Nature · doi:10.1038/nature08186 · Cited by 1,677 · see citing works
Population analysis of large copy number variants and hotspots of human genetic disease
Itsara, A., Cooper, G. M., Baker, C., Girirajan, S., Li, J., Absher, D., Krauss, R. M., Myers, R. M., Ridker, P. M., Chasman, D. I., et al. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.12.014 · Cited by 591 · see citing works
15q13.3 microdeletions increase risk of idiopathic generalized epilepsy.
Helbig, I., Mefford, H. C., Sharp, A. J., Guipponi, M., Fichera, M., Franke, A., Muhle, H., de Kovel, C., Baker, C., von Spiczak, S., et al. (2009) · Nature Genetics · doi:10.1038/ng.292 · Cited by 551 · see citing works
Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies
de Kovel, C. G. F., Trucks, H., Helbig, I., Mefford, H. C., Baker, C., Leu, C., Kluck, C., Muhle, H., von Spiczak, S., Ostertag, P., et al. (2010) · Brain · doi:10.1093/brain/awp262 · Cited by 445 · see citing works
Germline rates of de novo meiotic deletions and duplications causing several genomic disorders
Turner, D. J., Miretti, M., Rajan, D., Fiegler, H., Carter, N. P., Blayney, M. L., Beck, S., & Hurles, M. E. (2008) · Nature Genetics · doi:10.1038/ng.2007.40 · Cited by 320 · see citing works
Doornbos, M., Sikkema-Raddatz, B., Ruijvenkamp, C. A. L., Dijkhuizen, T., Bijlsma, E. K., Gijsbers, A. C. J., Hilhorst-Hofstee, Y., Hordijk, R., Verbruggen, K. T., Kerstjens-Frederikse, W. S. (., et al. (2009) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2009.03.010 · Cited by 165 · see citing works
Flagged first, then by citations
Research works printed but not linked: 26
- Zody, 2006, . Analysis of the DNA sequence and duplication history of human chromosome 15., Nature, 440, 671, 10.1038/nature04601 · DOI
- Chai, 2003, . Identification of four highly conserved genes between breakpoint hotspots BP1 and BP2 of the Prader-WilliAngelman syndromes deletion region that have undergone evolutionary transposition mediated by flanking duplicons., Am J Hum Genet, 73, 898, 10.1086/378816 · DOI · Paper page
- Butler, 2004, Behavioral differences among subjects with Prader-Willi syndrome and type I or type II deletion and maternal disomy., Pediatrics, 113, 565, 10.1542/peds.113.3.565 · DOI · Paper page
- Hartley, 2005, Maladaptive behaviors and risk factors among the genetic subtypes of Prader-Willi syndrome., Am J Med Genet A, 136, 140, 10.1002/ajmg.a.30771 · DOI · Paper page
- Sahoo, 2006, . Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations., J Med Genet, 43, 512, 10.1136/jmg.2005.036913 · DOI
- Kirov, 2009, ; International Schizophrenia Consortium; Wellcome Trust Case Control Consortium. Support for the involvement of large copy number variants in the pathogens is of schizophrenia., Hum Mo I Genet, 18, 1497, 10.1093/hmg/ddp043 · DOI · Paper page
- Mefford, 2009, . A method for rapid, targeted CNV genotyping identifies rare variants associated with neurocognitive disease., Genome Res, 19, 1579, 10.1101/gr.094987.109 · DOI · Paper page
- Burnside, 2011, . Microdeletionmicroduplication of proximal 15q11.2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay., Hum Genet, 130, 517, 10.1007/s00439-011-0970-4 · DOI · Paper page
- van der Zwaag, 2010, . A cosegregating microduplication of chromosome 15q11.2 pinpoints two risk genes for autism spectrum disorder., Am J Med Genet B Neuropsychiatr Genet, 153B, 960, 10.1002/ajmg.b.31055 · DOI · Paper page
- Reed, 2005, . A novel NIPA1 mutation associated with a pure form of autosomal dominant hereditary spastic paraplegia., Neurogenetics, 6, 79, 10.1007/s10048-004-0209-9 · DOI
- Nishimura, 2007, . Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways., Hum Mol Genet, 16, 1682, 10.1093/hmg/ddm116 · DOI · Paper page
- Nowicki, 2007, . The Prader-Willi phenotype of fragile X syndrome., J Dev Behav Pediatr, 28, 133, 10.1097/01.DBP.0000267563.18952.c9 · DOI · Paper page
- De Rubeis, 2011, Regulation of molecular pathways in the Fragile X Syndrome: insights into Autism Spectrum Disorders., J Neurodev Disord, 3, 257, 10.1007/s11689-011-9087-2 · DOI · Paper page
- Nagase, 2001, Prediction of the coding sequences of unidentified human genes. XXI. The complete sequences of 60 new cDNA clones from brain which code for large proteins., DNA Res, 8, 179, 10.1093/dnares/8.4.179 · DOI
- Francois, 2004, . Behavioural disorders induced by external globus pallidus dysfunction in primates II. Anatomical study., Brain, 127, 2055, 10.1093/brain/awh239 · DOI
- Grabli, 2004, . Behavioural disorders induced by external globus pallidus dysfunction in primates: I. Behavioural study., Brain, 127, 2039, 10.1093/brain/awh220 · DOI
- Yu, 2009, Validation of the Agilent 244K oligonucleotide array-based comparative genomic hybridization platform for clinical cytogenetic diagnosis., Am J Clin Pathol, 132, 349, 10.1309/AJCP1BOUTWF6ERYS · DOI
- Yu, 2009, Quantitative real-time polymerase chain reaction for the verification of genomic imbalances detected by microarray-based comparative genomic hybridization., Genet Test Mol Biomarkers, 13, 751, 10.1089/gtmb.2009.0056 · DOI
- 2008, Rare chromosomal deletions and duplications increase risk of schizophrenia., Nature, 455, 237, 10.1038/nature07239 · DOI · Paper page
- Burbach, 2009, Contact in the genetics of autism and schizophrenia., Trends Neurosci, 32, 69, 10.1016/j.tins.2008.11.002 · DOI
- Shen, 2010, ; Autism Consortium Clinical GeneticsDNA Diagnostics Collaboration. Clinical genetic testing for patients with autism spectrum disorders., Pediatrics, 125, e727, 10.1542/peds.2009-1684 · DOI · Paper page
- Tsang, 2009, . The hereditary spastic paraplegia proteins NIPA1, spastin and spartin are inhibitors of mammalian BMP signalling., Hum Mol Genet, 18, 3805, 10.1093/hmg/ddp324 · DOI
- Xiong, 2009, In vivo analysis of the functions of gamma-tubulin-complex proteins., J Cell Sci, 122, 4218, 10.1242/jcs.059196 · DOI
- Scoles, 2011, Increased copy number for methylated maternal 15q duplications leads to changes in gene and protein expression in human cortical samples., Mol Autism, 2, 19, 10.1186/2040-2392-2-19 · DOI
- Stewart, 2011, High frequency of known copy number abnormalities and maternal duplication 15q11-q13 in patients with combined schizophrenia and epilepsy., BMC Med Genet, 12, 154, 10.1186/1471-2350-12-154 · DOI
- Ingason, 2011, . Maternally derived microduplications at 15q11-q13: implication of imprinted genes in psychotic illness., Am J Psychiatry, 168, 408, 10.1176/appi.ajp.2010.09111660 · DOI · Paper page
Cited by
Sorted by citations
The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review
Cox, D., & Butler, M. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16024068 · Cited by 243 · see citing works
Clinical and genetic aspects of the 15q11.2 BP1–BP2 microdeletion disorder
Butler, M. G. (2017) · Journal of Intellectual Disability Research · doi:10.1111/jir.12382 · Cited by 102 · see citing works
- Authors
- Abdelmoity, A. T., LePichon, J.-B., Nyp, S. S., Soden, S. E., Daniel, C. A., & Yu, S.
- Affiliations
- Children's Mercy Hospital (US)
- Seattle Children's Hospital (US)
- Corresponding author
- Abdelmoity, Ahmed T.
- LePichon, Jean-Baptiste
- Venue
- Journal of Developmental & Behavioral Pediatrics
- Published
- 2012-09
- Volume
- 33
- Issue
- 7
- Pages
- 570-576
- ISSN
- 0196-206X (ISSN-L)
- OpenAlex
- W1987957217
- Cited by
- 44
- References
- 7
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 5 · 2018: 3 · 2017: 6 · 2016: 1 · 2015: 5 · 2014: 9 · 2013: 5
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Developmental & Behavioral Pediatrics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Keywords
- 15q11.2, intellectual disability, developmental delay, autism spectrum disorder, epilepsy, neuropsychiatric disorders, dysmorphic features, phenotypic spectrum, pediatric patients
- MeSH terms
- Congenital Abnormalities, Adolescent, Adult, Mental Disorders, Child, Developmental Disabilities, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 15, Female, Humans, Infant, Male, Intellectual Disability, Nervous System Diseases, Comparative Genomic Hybridization, Chromosome Duplication
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