{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T15:35:43Z","timestamp":1760369743702,"version":"build-2065373602"},"reference-count":78,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Phelan-McDermid syndrome (PMS) is a genetic disorder often characterized by autism or autistic-like behavior. Most cases are associated with haploinsufficiency of the SHANK3 gene resulting from deletion of the gene at 22q13.3 or from a pathogenic variant in the gene. Treatment of PMS often targets SHANK3, yet deletion size varies from &lt;50 kb to &gt;9 Mb, potentially encompassing dozens of genes and disrupting regulatory elements altering gene expression, inferring the potential for multiple therapeutic targets. Repurposed drugs have been used in clinical trials investigating therapies for PMS: insulin-like growth factor 1 (IGF-1) for its effect on social and aberrant behaviors, intranasal insulin for improvements in cognitive and social ability, and lithium for reversing regression and stabilizing behavior. The pharmacogenomics of PMS is complicated by the CYP2D6 enzyme which metabolizes antidepressants and antipsychotics often used for treatment. The gene coding for CYP2D6 maps to 22q13.2 and is lost in individuals with deletions larger than 8 Mb. Because PMS has diverse neurological and medical symptoms, many concurrent medications may be prescribed, increasing the risk for adverse drug reactions. At present, there is no single best treatment for PMS. Approaches to therapy are necessarily complex and must target variable behavioral and physical symptoms of PMS.<\/jats:p>","DOI":"10.3390\/genes12081192","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T12:59:24Z","timestamp":1627649964000},"page":"1192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Genetic Findings as the Potential Basis of Personalized Pharmacotherapy in Phelan-McDermid Syndrome"],"prefix":"10.3390","volume":"12","author":[{"given":"Brianna","family":"Dyar","sequence":"first","affiliation":[{"name":"Healthcare Genetics Program, School of Nursing, Clemson University, Clemson, SC 29634, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Meaddough","sequence":"additional","affiliation":[{"name":"Healthcare Genetics Program, School of Nursing, Clemson University, Clemson, SC 29634, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara M.","family":"Sarasua","sequence":"additional","affiliation":[{"name":"Healthcare Genetics Program, School of Nursing, Clemson University, Clemson, SC 29634, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Curtis","family":"Rogers","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29649, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katy","family":"Phelan","sequence":"additional","affiliation":[{"name":"Florida Cancer Specialists & Research Institute, Fort Myers, FL 33905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2017-4270","authenticated-orcid":false,"given":"Luigi","family":"Boccuto","sequence":"additional","affiliation":[{"name":"Healthcare Genetics Program, School of Nursing, Clemson University, Clemson, SC 29634, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,30]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Mirzaa, G., and Amemiya, A. (2005). Phelan-McDermid Syndrome. GeneReviews, University of Washington, Seattle. Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1198\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/1866-1955-6-39","article-title":"Phelan-McDermid syndrome: A review of the literatureand practice parameters for medical assessment and monitoring","volume":"6","author":"Kolevzon","year":"2014","journal-title":"J. Neurodev. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/2040-2392-4-18","article-title":"Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency","volume":"4","author":"Soorya","year":"2013","journal-title":"Mol. Autism"},{"key":"ref_4","first-page":"847","article-title":"Clinical and genomic evaluation of 201 patients with Phelan\u2013McDermid syndrome","volume":"133","author":"Sarasua","year":"2014","journal-title":"Qual. Life Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s11689-016-9150-0","article-title":"Developmental phenotype in Phelan-McDermid (22q13.3 deletion) syndrome: A systematic and prospective study in 34 children","volume":"8","author":"Zwanenburg","year":"2016","journal-title":"J. Neurodev. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14966","DOI":"10.1523\/JNEUROSCI.2215-12.2012","article-title":"Autism-Associated Mutations in ProSAP2\/Shank3 Impair Synaptic Transmission and Neurexin-Neuroligin-Mediated Transsynaptic Signaling","volume":"32","author":"Arons","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6525","DOI":"10.1523\/JNEUROSCI.6107-11.2012","article-title":"Reduced Excitatory Neurotransmission and Mild Autism-Relevant Phenotypes in Adolescent Shank3 Null Mutant Mice","volume":"32","author":"Yang","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1038\/s41380-018-0324-x","article-title":"An autism-linked missense mutation in SHANK3 reveals the modularity of Shank3 function","volume":"25","author":"Wang","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bonaglia, M.C., Giorda, R., Beri, S., De Agostini, C., Novara, F., Fichera, M., Grillo, L., Galesi, O., Vetro, A., and Ciccone, R. (2011). Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan\/McDermid Syndrome. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002173"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1136\/jmg.40.9.690","article-title":"Telomeric 22q13 deletions resulting from rings, simple deletions, and translocations: Cytogenetic, molecular, and clinical analyses of 32 new observations","volume":"40","author":"Luciani","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/jmg.40.8.575","article-title":"Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3\/PROSAP2 in the major neurological symptoms","volume":"40","author":"Wilson","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/jmedgenet-2011-100225","article-title":"Association between deletion size and important phenotypes expands the genomic region of interest in Phelan-McDermid syndrome (22q13 deletion syndrome)","volume":"48","author":"Sarasua","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_13","first-page":"1","article-title":"Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations","volume":"9","author":"Siper","year":"2018","journal-title":"Mol. Autism"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/ng1933","article-title":"Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders","volume":"39","author":"Durand","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1086\/522590","article-title":"Contribution of SHANK3 Mutations to Autism Spectrum Disorder","volume":"81","author":"Moessner","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/ajmg.b.30822","article-title":"Novel de novo SHANK3 mutation in autistic patients","volume":"150B","author":"Gauthier","year":"2008","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ejhg.2012.175","article-title":"Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders","volume":"21","author":"Boccuto","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Leblond, C.S., Nava, C., Polge, A., Gauthier, J., Huguet, G., Lumbroso, S., Giuliano, F., Stordeur, C., Depienne, C., and Mouzat, K. (2014). Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004580"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1002\/ajmg.a.36775","article-title":"De novoSHANK3mutation causes Rett syndrome-like phenotype in a female patient","volume":"167","author":"Hara","year":"2015","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"26697","DOI":"10.1074\/jbc.M112.424747","article-title":"SHANK3 Gene Mutations Associated with Autism Facilitate Ligand Binding to the Shank3 Ankyrin Repeat Region","volume":"288","author":"Mameza","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1002\/ajmg.a.36788","article-title":"Letter to the editor regarding Disciglio et al.: Interstitial 22q13 deletions not involving SHANK3 gene: A new contiguous gene syndrome","volume":"167","author":"Phelan","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1002\/ajmg.a.36513","article-title":"Interstitial 22q13 deletions not involving SHANK3 gene: A new contiguous gene syndrome","volume":"164","author":"Disciglio","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/ejhg.2008.107","article-title":"Interstitial 22q13 deletions: Genes other than SHANK3 have major effects on cognitive and language development","volume":"16","author":"Wilson","year":"2008","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104042","DOI":"10.1016\/j.ejmg.2020.104042","article-title":"Neurofibromatosis type 2 in Phelan-McDermid syndrome: Institutional experience and review of the literature","volume":"63","author":"Ziats","year":"2020","journal-title":"Eur. J. Med. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13148-020-00990-7","article-title":"DNA methylation epi-signature is associated with two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome","volume":"13","author":"Schenkel","year":"2021","journal-title":"Clin. Epigenet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41525-017-0035-2","article-title":"A framework to identify contributing genes in patients with Phelan-McDermid syndrome","volume":"2","author":"Tabet","year":"2017","journal-title":"NPJ Genom. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41431-017-0042-x","article-title":"Identification of 22q13 genes most likely to contribute to Phelan McDermid syndrome","volume":"26","author":"Mitz","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16486","DOI":"10.1038\/s41598-018-34729-5","article-title":"Brain volumetric alterations accompanied with loss of striatal medium-sized spiny neurons and cortical parvalbumin expressing interneurons in Brd1+\/\u2212 mice","volume":"8","author":"Qvist","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19544","DOI":"10.1038\/srep19544","article-title":"Mitochondrial Dysfunction may explain symptom variation in Phelan-McDermid Syndrome","volume":"6","author":"Frye","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1111\/cge.13451","article-title":"Variability in Phelan-McDermid syndrome: The impact of the PNPLA3 p.I148M polymorphism","volume":"94","author":"Boccuto","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/2045-8118-8-7","article-title":"Drug transport in brain via the cerebrospinal fluid","volume":"8","author":"Pardridge","year":"2011","journal-title":"Fluids Barriers CNS"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nn0602-849","article-title":"Sniffing neuropeptides: A transnasal approach to the human brain","volume":"5","author":"Born","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19141","DOI":"10.1073\/pnas.2002016117","article-title":"Targeting nanoparticles to the brain by exploiting the blood\u2013brain barrier impermeability to selectively label the brain endothelium","volume":"117","author":"Liu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-75253-9","article-title":"Investigating the optimum size of nanoparticles for their delivery into the brain assisted by focused ultrasound-induced blood\u2013brain barrier opening","volume":"10","author":"Ohta","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neubiorev.2016.01.001","article-title":"The therapeutic potential of insulin-like growth factor-1 in central nervous system disorders","volume":"63","author":"Costales","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"450","DOI":"10.3389\/fnins.2016.00450","article-title":"Insulin-Like Growth Factor 1 and Related Compounds in the Treatment of Childhood-Onset Neurodevelopmental Disorders","volume":"10","author":"Vahdatpour","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13229-019-0291-3","article-title":"Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: A systematic review of the literature","volume":"10","author":"Kolevzon","year":"2019","journal-title":"Mol. Autism"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/2040-2392-4-9","article-title":"Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay","volume":"4","author":"Bozdagi","year":"2013","journal-title":"Mol. Autism"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/2040-2392-5-54","article-title":"A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome","volume":"5","author":"Kolevzon","year":"2014","journal-title":"Mol. Autism"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sethuram, S., Kolevzon, A., and Rapaport, R. (2021, June 07). Growth Hormone Treatment in Children With Phelan McDermid Syndrome, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04003207?term=phelan-mcdermid&draw=1&rank=1.","DOI":"10.1186\/s13229-022-00485-7"},{"key":"ref_41","first-page":"1","article-title":"A case report of Phelan-McDermid syndrome: Preliminary results of the treatment with growth hormone therapy","volume":"47","author":"Xie","year":"2021","journal-title":"Ital. J. Pediatrics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1136\/jmg.2008.062141","article-title":"Intranasal insulin to improve developmental delay in children with 22q13 deletion syndrome: An exploratory clinical trial","volume":"46","author":"Schmidt","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1038\/ejhg.2016.109","article-title":"Is there an effect of intranasal insulin on development and behaviour in Phelan-McDermid syndrome? A randomized, dou-ble-blind, placebo-controlled trial","volume":"24","author":"Zwanenburg","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ebiom.2016.05.032","article-title":"Human Pluripotent Stem Cell-derived Cortical Neurons for High Throughput Medication Screening in Autism: A Proof of Concept Study in SHANK3 Haploinsufficiency Syndrome","volume":"9","author":"Darville","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/ajmg.a.35597","article-title":"Phelan-McDermid Syndrome: Clinical report of a 70-year-old woman","volume":"161","author":"Verhoeven","year":"2013","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_46","first-page":"S430","article-title":"Clinical case: Phelan\u2013McDermid and pharmacological management","volume":"41","author":"Ballesteros","year":"2020","journal-title":"Eur. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Serret, S., Thummler, S., Dor, E., Vesperini, S., Santos, A., and Askenazy, F. (2015). Lithium as a rescue therapy for regression and cata-tonia features in two SHANK3 patients with autism spectrum disorder: Case reports. BMC Psychiatry, 15.","DOI":"10.1186\/s12888-015-0490-1"},{"key":"ref_48","first-page":"bcr-2017","article-title":"Phelan-McDermid syndrome due to SHANK3 muta-tion in an intellectually disabled adult male: Successful treatment with lithium","volume":"2017","author":"Egger","year":"2017","journal-title":"BMJ Case Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/bld.12235","article-title":"Phelan-McDermid syndrome, bipolar disorder and treatment with lithium","volume":"46","author":"Rowland","year":"2018","journal-title":"Br. J. Learn. Disabil."},{"key":"ref_50","unstructured":"Delorme, R. (2021, June 07). Effect of Lithium in Patients with Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Hap-loinsufficiency) (Lisphem), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04623398?term=therapy+OR+treatment+OR+clinical+trial&cond=Phelan-McDermid+Syndrome&draw=1&rank=7."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.psychres.2018.03.061","article-title":"Coenzyme Q10 supple-mentation reduces oxidative stress and decreases antioxidant enzyme activity in children with autism spectrum disorders","volume":"265","author":"Mousavinejad","year":"2018","journal-title":"Psychiatry Res."},{"key":"ref_52","unstructured":"Persico, A.M. (2021, June 07). Q10 Ubiquinol in Autism Spectrum Disorder and in Phelan-McDermid Syndrome. (Q10ASD), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04312152?term=therapy+OR+treatment+OR+clinical+trial&cond=Phelan-McDermid+Syndrome&draw=1&rank=6."},{"key":"ref_53","unstructured":"Kolevzon, A. (2021, June 07). AMO-01 to Treat Adolescents and Adults With Phelan-McDermid Syndrome (PMS) and Co-morbid Epilepsy, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03493607?term=phelan-mcdermid&draw=1&rank=7."},{"key":"ref_54","unstructured":"Kolevzon, A. (2021, June 07). Piloting Treatment With Intranasal Oxytocin in Phelan-McDermid Syndrome, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02710084?term=phelan-mcdermid&draw=1&rank=5."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1146\/annurev-pharmtox-010919-023508","article-title":"Addressing the Challenge of Polypharmacy","volume":"60","author":"Mair","year":"2020","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7863","DOI":"10.1073\/pnas.0906232107","article-title":"De novo mutations in the gene encoding the synaptic scaffolding proteinSHANK3in patients ascertained for schizophrenia","volume":"107","author":"Gauthier","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Wan, L., Liu, D., Xiao, W.-B., Zhang, B.-X., Yan, X.-X., Luo, Z.-H., and Xiao, B. (2021). Association of SHANK Family with Neuropsychiatric Disorders: An Update on Genetic and Animal Model Discoveries. Cell. Mol. Neurobiol., 1\u201321.","DOI":"10.1007\/s10571-021-01054-x"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Zdanowicz, M.M. (2017). Central Nervous System. Concepts in Pharmacogenomics, American Society of Health-System Pharmacists. [2nd ed.].","DOI":"10.37573\/9781585285174"},{"key":"ref_59","first-page":"1","article-title":"Pharmacogenetics of Antipsychotic Drug Treatment: Update and Clinical Implications","volume":"5","author":"Yoshida","year":"2019","journal-title":"Mol. Neuropsychiatry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1055\/a-1288-1061","article-title":"Review and Consensus on Pharmacogenomic Testing in Psychiatry","volume":"54","author":"Bousman","year":"2021","journal-title":"Pharmacopsychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/cpt.1004","article-title":"Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update","volume":"103","author":"Phillips","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_62","unstructured":"PharmGKB (2021, July 25). Annotation of FDA Label for aripiprazole and CYP2D6. Available online: https:\/\/www.pharmgkb.org\/labelAnnotation\/PA166104839."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Klomp, S.D., Manson, M.L., Guchelaar, H.J., and Swen, J.J. (2020). Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092890"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"38","DOI":"10.2174\/1389450118666170125144557","article-title":"Cytochrome P450 Structure, Function and Clinical Significance: A Review","volume":"19","author":"Manikandan","year":"2018","journal-title":"Curr. Drug Targets"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Taylor, C., Crosby, I., Yip, V., Maguire, P., Pirmohamed, M., and Turner, R.M. (2020). A Review of the Important Role of CYP2D6 in Pharmacogenomics. Genes, 11.","DOI":"10.3390\/genes11111295"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/cpt.597","article-title":"Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update","volume":"102","author":"Hicks","year":"2017","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_67","unstructured":"Food and Drug Association (2021, July 25). Table of Pharmacogenetic Associations, Available online: https:\/\/www.fda.gov\/medical-devices\/precision-medicine\/table-pharmacogenetic-associations."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/cpt.1409","article-title":"Clinical Pharmacogenetics Implementation Consortium Guideline for Cytochrome P450 (CYP) 2D6 Genotype and Atomoxetine Therapy","volume":"106","author":"Brown","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.gpb.2015.01.002","article-title":"Web resources for pharmacogenomics","volume":"13","author":"Zhang","year":"2015","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kim, J.A., Ceccarelli, R., and Lu, C.Y. (2021). Pharmacogenomic Biomarkers in US FDA-Approved Drug Labels. J. Pers. Med., 11.","DOI":"10.3390\/jpm11030179"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"103751","DOI":"10.1016\/j.ejmg.2019.103751","article-title":"A longitudinal perspective on the pharmacotherapy of 24 adult patients with Phelan McDermid syndrome","volume":"63","author":"Verhoeven","year":"2020","journal-title":"Eur. J. Med. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/gbb.12285","article-title":"Neuropsychological phenotype and psychopathology in seven adult patients with Phelan-McDermid syndrome: Implications for treatment strategy","volume":"15","author":"Egger","year":"2016","journal-title":"Genes Brain Behav."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1111\/epi.13506","article-title":"The spectrum of epilepsy and electroencephalographic abnormalities due to SHANK3 loss-of-function mutations","volume":"57","author":"Holder","year":"2016","journal-title":"Epilepsia"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s11689-020-9309-6","article-title":"Psychiatric illness and regression in individuals with Phelan-McDermid syndrome","volume":"12","author":"Kohlenberg","year":"2020","journal-title":"J. Neurodev. Disord."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/cpt.147","article-title":"Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline forCYP2D6andCYP2C19Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors","volume":"98","author":"Hicks","year":"2015","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/cpt.2008","article-title":"Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update","volume":"109","author":"Karnes","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/cge.13178","article-title":"A critical appraisal of pharmacogenetic inference","volume":"93","author":"Smit","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Hippman, C., and Nislow, C. (2019). Pharmacogenomic Testing: Clinical Evidence and Implementation Challenges. J. Pers. Med., 9.","DOI":"10.3390\/jpm9030040"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/8\/1192\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:37:57Z","timestamp":1760164677000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/8\/1192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,30]]},"references-count":78,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["genes12081192"],"URL":"https:\/\/doi.org\/10.3390\/genes12081192","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2021,7,30]]}}}