Rare Pathogenic Copy Number Variation in the 16p11.2 (BP4–BP5) Region Associated with Neurodevelopmental and Neuropsychiatric Disorders: A Review of the Literature
Abstract
:1. Introduction
2. Materials and Methods
2.1. Searching Strategy
2.2. Study Selection: Inclusion and Exclusion Criteria
2.3. Data Extraction
3. Results
3.1. Review of the Literature
3.2. Proximal Deletions
3.3. Proximal Duplications
4. Discussion
Future Perspectives
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Thapar, A.; Cooper, M. Copy Number Variation: What Is It and What. J. Am. Acad. Child Adolesc. Psychiatry 2013, 52, 772–774. [Google Scholar] [CrossRef][Green Version]
- Jutla, A.; Turner, J.B.; Snyder, L.G.; Chung, W.K.; Veenstra-VanderWeele, J. Psychotic symptoms in 16p11.2 copy-number variant carriers. Autism Res. 2019, 13, 187–198. [Google Scholar] [CrossRef]
- Orphanet. Available online: http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=12136&Disease_Disease_Search_diseaseGroup=hae&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group of diseases=Hereditary-angioedema--HAE-&title=Hereditary-angioedema--HAE-&search=Di (accessed on 22 July 2020).
- Zufferey, F.; Sherr, E.H.; Beckmann, N.D.; Hanson, E.; Maillard, A.M.; Hippolyte, L.; Macé, A.; Ferrari, C.; Kutalik, Z.; Andrieux, J.; et al. A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders. J. Med Genet. 2012, 49, 660–668. [Google Scholar] [CrossRef]
- Weiss, L.; Shen, Y.; Korn, J.M.; Arking, D.E.; Miller, D.T.; Fossdal, R.; Saemundsen, E.; Stefansson, H.; Ferreira, M.A.; Green, T.; et al. Association between Microdeletion and Microduplication at 16p11.2 and Autism. New Engl. J. Med. 2008, 358, 667–675. [Google Scholar] [CrossRef][Green Version]
- Jacquemont, S.; Reymond, A.; Zufferey, F.; Harewood, L.; Walters, R.G.; Kutalik, Z.; Martinet, D.; Shen, Y.; Valsesia, A.; Beckmann, N.D.; et al. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus. Nat. Cell Biol. 2011, 478, 97–102. [Google Scholar] [CrossRef][Green Version]
- Hudac, C.M.; Bove, J.; Barber, S.; Duyzend, M.; Wallace, A.; Martin, C.L.; Ledbetter, D.H.; Hanson, E.; Goin-Kochel, R.P.; Green-Snyder, L.; et al. Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers. Autism Res. 2020. [Google Scholar] [CrossRef]
- D’Angelo, D.; Lebon, S.; Chen, Q.; Martin-Brevet, S.; Snyder, L.G.; Hippolyte, L.; Hanson, E.; Maillard, A.M.; Faucett, W.A.; Macé, A.; et al. Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities. JAMA Psychiatry 2016, 73, 20–30. [Google Scholar] [CrossRef] [PubMed]
- Genetics Home Reference. Available online: https://ghr.nlm.nih.gov/condition/16p112-duplication#statistics (accessed on 20 August 2020).
- Sanders, K.B.S.J.; Ercan-Sencicek, A.G.; Hus, V.; Luo, R.; Murtha, M.T.; Moreno-De-Luca, D.; Chu, S.H.; Moreau, M.P.; Gupta, A.R.; Thomson, S.A.; et al. Multiple recurrent de novo copy number variations (CNVs), including duplications of the 7q11.23 Williams-Beuren syndrome region, are strongly associated with autism. Neuron 2011, 70, 863–885. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Kumar, R.A.; Karamohamed, S.; Sudi, J.; Conrad, D.F.; Brune, C.; Badner, J.A.; Gilliam, T.C.; Nowak, N.J.; Cook, E.H.; Dobyns, W.B.; et al. Recurrent 16p11.2 microdeletions in autism. Hum. Mol. Genet. 2007, 17, 628–638. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Marshall, C.R.; Noor, A.; Vincent, J.B.; Lionel, A.C.; Feuk, L.; Skaug, J.; Shago, M.; Moessner, R.; Pinto, D.; Ren, Y.; et al. Structural Variation of Chromosomes in Autism Spectrum Disorder. Am. J. Hum. Genet. 2008, 82, 477–488. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Rees, E.; Walters, J.T.R.; Georgieva, L.; Isles, A.R.; Chambert, K.D.; Richards, A.L.; Mahoney-Davies, G.; Legge, S.E.; Moran, J.L.; McCarroll, S.A.; et al. Analysis of copy number variations at 15 schizophrenia-associated loci. Br. J. Psychiatry 2014, 204, 108–114. [Google Scholar] [CrossRef] [PubMed]
- Hanson, E.; Bernier, R.; Porche, K.; Jackson, F.I.; Goin-Kochel, R.P.; Snyder, L.G.; Snow, A.V.; Wallace, A.S.; Campe, K.L.; Zhang, Y.; et al. The Cognitive and Behavioral Phenotype of the 16p11.2 Deletion in a Clinically Ascertained Population. Biol. Psychiatry 2015, 77, 785–793. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Kvarnung, M.; Nordgren, A. Intellectual Disability & Rare Disorders: A Diagnostic Challenge. Atherosclerosis 2017, 1031, 39–54. [Google Scholar] [CrossRef]
- Shinawi, M.; Liu, P.; Kang, S.-H.L.; Shen, J.; Belmont, J.W.; Scott, D.; Probst, F.J.; Craigen, W.J.; Graham, B.H.; Pursley, A.; et al. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. J. Med Genet. 2010, 47, 332–341. [Google Scholar] [CrossRef]
- OMIN. Available online: https://omim.org/ (accessed on 20 August 2020).
- GTEx Expression Data. Available online: https://www.gtexportal.org/home/ (accessed on 20 August 2020).
- The Genome Aggregation Database. Available online: https://gnomad.broadinstitute.org/ (accessed on 20 August 2020).
- Fernandez, B.; Roberts, W.S.; Chung, B.; Weksberg, R.; Meyn, S.; Szatmari, P.; Joseph-George, A.M.; Mackay, S.; Whitten, K.; Noble, B.; et al. Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder. J. Med Genet. 2009, 47, 195–203. [Google Scholar] [CrossRef][Green Version]
- Rosenfeld, J.A.; Coppinger, J.; Bejjani, B.A.; Girirajan, S.; Eichler, E.E.; Shaffer, L.G.; Ballif, B.C. Speech delays and behavioral problems are the predominant features in individuals with developmental delays and 16p11.2 microdeletions and microduplications. J. Neurodev. Disord. 2009, 2, 26–38. [Google Scholar] [CrossRef][Green Version]
- Goin-Kochel, R.P.; Hudac, C.M.; Chen, Q.; Zeng, C.; Wallace, A.S.; Gerdts, J.; Earl, R.; Peterson, J.; Wolken, A.; Peters, A.; et al. Developmental trajectories for young children with 16p11.2 copy number variation. Am. J. Med. Genet. Part B Neuropsychiatr. Genet. 2017, 174, 367–380. [Google Scholar] [CrossRef]
- Niarchou, M.; Chawner, S.J.; Doherty, J.L.; Maillard, A.M.; Jacquemont, S.; Chung, W.K.; Green-Snyder, L.; Bernier, R.A.; Goin-Kochel, R.P.; Hanson, E.; et al. Psychiatric disorders in children with 16p11.2 deletion and duplication. Transl. Psychiatry 2019, 9, 1–8. [Google Scholar]
- Hippolyte, L.; Maillard, A.M.; Rodriguez-Herreros, B.; Pain, A.; Martin-Brevet, S.; Ferrari, C.; Conus, P.; Macé, A.; Hadjikhani, N.; Metspalu, A.; et al. The Number of Genomic Copies at the 16p11.2 Locus Modulates Language, Verbal Memory, and Inhibition. Biol. Psychiatry 2016, 80, 129–139. [Google Scholar] [CrossRef][Green Version]
- Snyder, L.G.; D’Angelo, D.; Chen, Q.; Bernier, R.; Goin-Kochel, R.P.; Wallace, A.S.; Gerdts, J.; Kanne, S.; Berry, L.; Blaskey, L.; et al. Autism Spectrum Disorder, Developmental and Psychiatric Features in 16p11.2 Duplication. J. Autism Dev. Disord. 2016, 46, 2734–2748. [Google Scholar] [CrossRef]
- The Simons VIP Consortium. Simons Variation in Individuals Project (Simons VIP): A Genetics-First Approach to Studying Autism Spectrum and Related Neurodevelopmental Disorders. Neuron 2012, 73, 1063–1067. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Shadan, K.; Rodriguez, E.A. Available online. Met. Powder Rep. 2008, 63, 11. [Google Scholar] [CrossRef]
- McCarthy, S.; Makarov, V.; Kirov, G.; Addington, A.M.; McClellan, J.; Yoon, S.; Perkins, D.; Dickel, D.E.; Kusenda, M.; Krause, V. Microduplications of 16p11.2 are associated with schizophrenia. Nat. Genet. 2009, 41, 1223–1227. [Google Scholar] [CrossRef] [PubMed]
- Marshall, C.R.; Howrigan, D.P.; Merico, D.; Thiruvahindrapuram, B.; Wu, W.; Greer, D.S.; Antaki, D.; Shetty, A.; Holmans, P.A.; Pinto, D.; et al. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects. Nat. Genet. 2017, 49, 27–35. [Google Scholar] [CrossRef][Green Version]
- Chang, Y.S.; Owen, J.P.; Pojman, N.J.; Thieu, T.; Bukshpun, P.; Wakahiro, M.L.; Marco, E.J.; Berman, J.I.; Spiro, J.E.; Chung, W.K.; et al. Reciprocal white matter alterations due to 16p11.2 chromosomal deletions versus duplications. Hum. Brain Mapp. 2016, 37, 2833–2848. [Google Scholar] [CrossRef][Green Version]
- Bijlsma, E.; Gijsbers, A.C.J.; Schuurs-Hoeijmakers, J.H.M.; Van Haeringen, A.; Van De Putte, D.E.F.; Anderlid, B.-M.; Lundin, J.; Lapunzina, P.; Jurado, L.A.P.; Chiaie, B.D.; et al. Extending the phenotype of recurrent rearrangements of 16p11.2: Deletions in mentally retarded patients without autism and in normal individuals. Eur. J. Med. Genet. 2009, 52, 77–87. [Google Scholar] [CrossRef]
- Ghebranious, N.; Giampietro, P.F.; Wesbrook, F.P.; Rezkalla, S.H. A novel microdeletion at 16p11.2 harbors candidate genes for aortic valve development, seizure disorder, and mild mental retardation. Am. J. Med. Genet. Part A 2007, 221, 1462–1471. [Google Scholar] [CrossRef]
- Human Phenotype Ontology. Available online: https://hpo.jax.org/app (accessed on 20 August 2020).
- Kirov, G.; Rees, E.; Walters, J.T.; Escott-Price, V.; Georgieva, L.; Richards, A.L.; Chambert, K.D.; Davies, G.; Legge, S.E.; Moran, J.L.; et al. The Penetrance of Copy Number Variations for Schizophrenia and Developmental Delay. Biol. Psychiatry 2014, 75, 378–385. [Google Scholar] [CrossRef][Green Version]
- NCIt. Available online: https://www.ebi.ac.uk/ols/ontologies/ncit (accessed on 20 August 2020).
- Moreno-De-Luca, A.; Evans, D.W.; Boomer, K.B.; Hanson, E.; Bernier, R.; Goin-Kochel, R.P.; Myers, S.M.; Challman, T.D.; Moreno-De-Luca, D.; Slane, M.M.; et al. The role of parental cognitive, behavioral, and motor profiles in clinical variability in individuals with chromosome 16p11.2 deletions. JAMA Psychiatry 2015, 72, 119–126. [Google Scholar] [CrossRef]
- Duyzend, M.H.; Nuttle, X.; Coe, B.P.; Baker, C.; Nickerson, D.A.; Bernier, R.; Eichler, E.E. Maternal Modifiers and Parent-of-Origin Bias of the Autism-Associated 16p11.2 CNV. Am. J. Hum. Genet. 2016, 98, 45–57. [Google Scholar] [CrossRef][Green Version]
- Girirajan, P.D.S.; Rosenfeld, J.A.; Coe, B.P.; Parikh, S.; Friedman, N.; Goldstein, A.; Filipink, R.A.; McConnell, J.S.; Angle, B.; Meschino, W.S.; et al. Phenotypic Heterogeneity of Genomic Disorders and Rare Copy- Number Variants. N. Engl. J. Med. 2013, 367, 1321–1331. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Redaelli, S.; Maitz, S.; Crosti, F.; Sala, E.; Villa, N.; Spaccini, L.; Selicorni, A.; Rigoldi, M.; Conconi, D.; Dalpra, L.; et al. Refining the Phenotype of Recurrent Rearrangements of Chromosome 16. Int. J. Mol. Sci. 2019, 20, 1095. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Horev, G.; Ellegood, J.; Lerch, J.P.; Son, Y.-E.E.; Muthuswamy, L.; Vogel, H.; Krieger, A.M.; Buja, A.; Henkelman, R.M.; Wigler, M.; et al. Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism. Proc. Natl. Acad. Sci. USA 2011, 108, 17076–17081. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Drakulic, D.; Djurovic, S.; Syed, Y.A.; Trattaro, S.; Caporale, N.; Falk, A.; Ofir, R.; Heine, V.M.; Chawner, S.J.R.A.; Rodriguez-Moreno, A.; et al. Copy number variants (CNVs): A powerful tool for iPSC-based modelling of ASD. Mol. Autism 2020, 11. [Google Scholar] [CrossRef]
- Deshpande, A.; Yadav, S.; Dao, D.Q.; Wu, Z.Y.; Hokanson, K.C.; Cahill, M.K.; Wiita, A.P.; Jan, Y.-N.; Ullian, E.M.; Weiss, L.A.; et al. Cellular phenotypes in human iPSC-derived neurons from a genetic model of autism spectrum disorder. Cell Rep. 2017, 21, 2678–2687. [Google Scholar] [CrossRef][Green Version]
- Tai, D.J.C.; Ragavendran, A.; Manavalan, P.; Stortchevoi, A.; Seabra, C.M.; Erdin, S.; Collins, R.L.; Blumenthal, I.; Chen, X.; Shen, Y.; et al. Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR. Nat. Neurosci. 2016, 19, 517–522. [Google Scholar] [CrossRef]
Syndrome Name | ORPHA ID | Chromosomal Location |
---|---|---|
16p11.2p12.2 microdeletion syndrome | 261211 | Del(16)(p11.2p12.2) |
16p11.2p12.2 microduplication syndrome | 261204 | Dup(16)(p11.2p12.2) |
Distal 16p11.2 microdeletion syndrome | 261222 | Distal del(16)(p11.2) |
Proximal 16p11.2 microdeletion syndrome | 261197 | Proximal del(16)(p11.2) |
Proximal 16p11.2 microduplication syndrome | 370079 | Proximal dup(16)(p11.2) |
Data Source | Ascertainment (16p11.2) | Age Range | Gender (M/F) | Cognition | Speech and Language Problems | Neurodevelopmental Disorders | Psychosis | Seizures | Behavioural Problems | Other Mental Disorders | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ID/DD | Delay | Nonvverbal | Articulation | ASD Diagnosis | ASD Features | ADHD | AD Features | Schizophrenia | Other Features | ODD, Aggression | Anxiety | Depression | Obsessions | Phobias | Other | |||||
Fernandez et al. 2010 | Diagnosis of ASD | 5–18 y | 2/1 | 3/3 | 2/3 | 1/3 | N/P | 3/3 | 0/3 | 1/3 | 0/3 | 0/3 | 0/3 | N/P | 0/3 | 1/3 | 1/3 | 0/3 | 0/3 | 0/3 |
Rosenfeld et al. 2010 | Developmental delays, ASD, dysmorphism, congenital anomalies, seizures | 0.4–20 y | 8/6 | 13/14 | 9/14 | 2/14 | 1/14 (i) | 0/14 | 7/14 | 0/14 | 7/14 | 0/14 | 0/14 (j) | 0/14 (k) | 5/14 | 2/14 | 1/14 | 1/14 | 2/14 | 2/14 |
Shinawi et al. 2010 | Diverse reasons for referral | 0.6–9 y | 10/5 | 13/13 | 15/15 | 1/13 | N/P | 2/10 | 2/10 | 4/10 | 1/10 | N/P | N/P | 5/15 (l) | 2/10 | N/P | N/P | N/P | N/P | N/P |
Zufferey et al. 2012 | Simons VIP consortium + 16p11.2 European Consortium | 10.7 (a) | 56/28 | About 20%of carriers meeting criteria for ID (Intelligence-2SD) | History of speech therapy in 83% of all carriers (n = 285) | N/P | N/P | 8/55 (15%) (e) | N/P | N/P | N/P | N/P | N/P | 24% | 51/70 (g) | |||||
Hanson et al. 2015 | Simons VIP consortium + Cascade testing | 3–17 y | 78 (d) | 8/78 (ID,10%) 10/78 (DD,13%) | 44 (56%) | N/P | 36/78 (46%) | 20/78 (26%) | N/P | 15/78 (19%) | N/P | N/P | Tic disorder 5(6%), Learning disorders 10/78 (13%) | N/P | 10/78 (13%) | 5/78 (6%) | N/P | N/P | N/P | N/P |
Hyppolyte et al. 2016 | Mostly European 16p11.2 cohort + Cascade testing + Estonian and replication cases from SimonsVIP consortium | 4.8–59 y | 35/27 | Range reported only | Range reported (phonological skills, lexical skills, written language, and comprehension and verbal skills) | 3/62 | N/P | N/P | N/P | 0/62 | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | ||
D’Angelo et al. 2016 | Simons VIP consortium + 16p11.2 European Consortium | 7.6 (4.9) (b) 16.5 (15.9) (c) | 187/130 | N/P | N/P | N/P | N/P | 51/317 | N/P | N/P | N/P | 0/317 | N/P | 69/317 (21.8%) | 157/317 (h) | |||||
Bernier et al. 2017 | SimonsVIP consortium | 0,5-5y | 18/15 | 5/33 (15%) | 18/33(54%) | N/P | 22/33 (67%) | 8/33 (24%) | N/P | 8/33 (24%) | N/P | N/P | 2/33 (67%) (f) | N/P | 3/33 (9%) | 2/33 (6%) | N/P | N/P | N/P | N/P |
Niarchou et al. 2019 | Simons VIP consortium + 16p11.2 European consortium | 4.8–17.7 y | N/P | 51/193 | N/P | N/P | N/P | 39/193 | N/P | 59/193 | N/P | 0/193 | 9/193 | N/P | 13/193 | 18/193 | 0/193 | 2/193 | 17/193 | 1/193 |
Hudac et al. 2020 | Simons VIP consortium + cascade testing | 0.8–20.8 y | 46/43 | Mean and SD reportedonly | N/P | N/P | N/P | 21/89 (23.6%) | Mean and SD reportedonly | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P |
Kim et al. 2020 | Simons Searchlight | 2–23 y | 53/57 | N/P | 63-84% (m) | N/P | N/P | 26/110 (23.6%) | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P |
Data Source | Ascertainment (16p11.2) | Age Range | Gender M/F | Cognition | Speech and Language Problems | Neurodevelopmental Disorders | Psychosis | Seizures | Behavioural Problems | Other Mental Disorders | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ID/DD | Regression | Delay | Nonverbal | Articulation | ASD Diagnosis | ASD Features | ADHD | AD Features | Other NDDs | Schizophrenia | Other Features | ODD, Aggression | Anxiety | Depression | Obsessions | Phobias | Other | |||||
Fernandez et al. 2010 | All cases ascertained on the basis of a diagnosis of ASD | 2.2–15.5y | 1/2 | 1/14 (MR) | 3/3 | 2 (1 NT) | 2 (1 NT) | 2/3 | 2/3 | 1/3 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 | 1/3 (h) | 0/3 | 1/3 | 0/3 | 0/3 | 0/3 | 0/3 |
Rosenfeld et al. 2010 | Developmental delays, ASD, dysmorphism, congenitalanomalies, seizures | 1–7 y | 6/1 | 6/7 | 1/7(j) | 4/7 | 0/7 | 0/7 | 1/7 | 0/7 | 0/7 | 2/7 | N/P | N/P | N/P | 0/7 (i) | 2/7 | 0/7 | N/P | 0/7 | 0/7 | 0/7 |
Shinawi et al. 2010 | Diverse reasons for referral | 4–13 y | 5/2 | 6/7 | 0/7 | 6/7 | 0/7 | 1/7 | 0/7 | 1/7 | 5/7 | 0/7 | N/P | N/P | N/P | 3/7 | 2/7 | N/P | N/P | N/P | N/P | N/P |
Snyder et al. 2016 | Clinical, online recruitment and laboratory referrals | 1.1–17.3 y (46) | 26/20 | 19/46 (41%) | N/P | N/P | N/P | 10/46 (22%) | 11/46 (24%) | 12/46 (26%) | N/P | 2/46 (4.4%) (a) | N/P | 25/46 (54%) (e) | N/P | 6/46 (13%) | 8/46 (17.4%) (d) | N/P | N/P | N/P | 2/46 (4%) (c) | |
D’Angelo et al. 2016 | Simons VIP consortium + 16p11.2 European Consortium | 9.1 (8.8) (f)–24.2 (21.9) (g) | 104/7 6 | N/P | N/P | N/P | N/P | N/P | 36/180 | N/P | N/P | N/P | N/P | 4/180 | N/P | 35/180 (19.4%) | 71/180 (b) | |||||
Bernier et al. 2017 | Simons VIP consortium | 0.5–5 y | 13/10 | 5/230 (22%) | N/P | 6/2 (26%) | N/P | 8/2 (35%) | 5/23 22% | N/P | 9/23 (39%) | N/P | N/P | N/P | 13/23 (56%) (e) | N/P | 7/23 (30%) | 1/23 (4%) | N/P | N/P | N/P | N/P |
Niarchou et al. 2019 | Simons VIP consortium + European 16p11.2 consortium | 3.1–17.3 y | N/P | 31/89 | N/P | N/P | N/P | N/P | 24/89 | N/P | 39/89 | N/P | N/P | 0/89 | 8/89 | N/P | 11/89 | 10/89 | 0/89 | 2/89 | 8/89 | 2/89 |
Hudac et al. 2020 | Simons VIP consortium | 1.7–23.4 y | 17/24 | Mean and SD reported only | N/P | N/P | N/P | N/P | 9/41 (22%) | Mean and SD reported only | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P |
Kim et al. 2020 | Simons Searchlight | 2–23 y | 34/24 | N/P | N/P | 46–96 % (k) | N/P | N/P | 13/58 (22.4%) | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P | N/P |
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Oliva-Teles, N.; de Stefano, M.C.; Gallagher, L.; Rakic, S.; Jorge, P.; Cuturilo, G.; Markovska-Simoska, S.; Borg, I.; Wolstencroft, J.; Tümer, Z.; et al. Rare Pathogenic Copy Number Variation in the 16p11.2 (BP4–BP5) Region Associated with Neurodevelopmental and Neuropsychiatric Disorders: A Review of the Literature. Int. J. Environ. Res. Public Health 2020, 17, 9253. https://doi.org/10.3390/ijerph17249253
Oliva-Teles N, de Stefano MC, Gallagher L, Rakic S, Jorge P, Cuturilo G, Markovska-Simoska S, Borg I, Wolstencroft J, Tümer Z, et al. Rare Pathogenic Copy Number Variation in the 16p11.2 (BP4–BP5) Region Associated with Neurodevelopmental and Neuropsychiatric Disorders: A Review of the Literature. International Journal of Environmental Research and Public Health. 2020; 17(24):9253. https://doi.org/10.3390/ijerph17249253
Chicago/Turabian StyleOliva-Teles, Natália, Maria Chiara de Stefano, Louise Gallagher, Severin Rakic, Paula Jorge, Goran Cuturilo, Silvana Markovska-Simoska, Isabella Borg, Jeanne Wolstencroft, Zeynep Tümer, and et al. 2020. "Rare Pathogenic Copy Number Variation in the 16p11.2 (BP4–BP5) Region Associated with Neurodevelopmental and Neuropsychiatric Disorders: A Review of the Literature" International Journal of Environmental Research and Public Health 17, no. 24: 9253. https://doi.org/10.3390/ijerph17249253