{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:59:17Z","timestamp":1792205957862,"version":"4.4.0"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T00:00:00Z","timestamp":1560470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["U54 HD 090216"],"award-info":[{"award-number":["U54 HD 090216"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The 15q11.2 BP1\u2013BP2 microdeletion (Burnside\u2013Butler) syndrome is an emerging disorder that encompasses four genes (NIPA1, NIPA2, CYFIP1, and TUBGCP5). When disturbed, these four genes can lead to cognitive impairment, language and\/or motor delay, psychiatric\/behavioral problems (attention-deficit hyperactivity, autism, dyslexia, schizophrenia\/paranoid psychosis), ataxia, seizures, poor coordination, congenital anomalies, and abnormal brain imaging. This microdeletion was reported as the most common cytogenetic finding when using ultra-high- resolution chromosomal microarrays in patients presenting for genetic services due to autism with or without additional clinical features. Additionally, those individuals with Prader\u2013Willi or Angelman syndromes having the larger typical 15q11\u2013q13 type I deletion which includes the 15q11.2 BP1\u2013BP2 region containing the four genes, show higher clinical severity than those having the smaller 15q11\u2013q13 deletion where these four genes are intact. Two of the four genes (i.e., NIPA1 and NIPA2) are expressed in the brain and encode magnesium transporters. Magnesium is required in over 300 enzyme systems that are critical for multiple cellular functions, energy expenditure, protein synthesis, DNA transcription, and muscle and nerve function. Low levels of magnesium are found in those with seizures, depression, and acute or chronic brain diseases. Anecdotally, parents have administered magnesium supplements to their children with the 15q11.2 BP1\u2013BP2 microdeletion and have observed improvement in behavior and clinical presentation. These observations require more attention from the medical community and should include controlled studies to determine if magnesium supplements could be a treatment option for this microdeletion syndrome and also for a subset of individuals with Prader\u2013Willi and Angelman syndromes.<\/jats:p>","DOI":"10.3390\/ijms20122914","type":"journal-article","created":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T11:19:58Z","timestamp":1560511198000},"page":"2914","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Magnesium Supplement and the 15q11.2 BP1\u2013BP2 Microdeletion (Burnside\u2013Butler) Syndrome: A Potential Treatment?"],"prefix":"10.3390","volume":"20","author":[{"given":"Merlin G.","family":"Butler","sequence":"first","affiliation":[{"name":"Departments of Psychiatry &amp; Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1542\/peds.113.3.565","article-title":"Behavioral differences among subjects with Prader-Willi syndrome and type I or type II deletion and maternal disomy","volume":"113","author":"Butler","year":"2004","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1097\/GIM.0b013e3181def138","article-title":"Clinical and genetic aspects of Angelman syndrome","volume":"12","author":"Williams","year":"2010","journal-title":"Genet. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/342281a0","article-title":"Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome","volume":"342","author":"Nicholls","year":"1989","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/ajmg.1320350306","article-title":"Prader-Willi syndrome: Current understanding of cause and diagnosis","volume":"35","author":"Butler","year":"1990","journal-title":"Am. J. Med. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Butler, M.G., Lee, P.D.K., and Whitman, B.Y. (2006). Management of Prader-Willi Syndrome, Springer.","DOI":"10.1007\/978-0-387-33536-0"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1462399405009531","article-title":"Prader-Willi syndrome: Clinical genetics, cytogenetics and molecular biology","volume":"7","author":"Bittel","year":"2005","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/gim.0b013e31822bead0","article-title":"Prader-Willi syndrome","volume":"14","author":"Cassidy","year":"2012","journal-title":"Genet. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1007\/s40618-015-0312-9","article-title":"Prader-Willi syndrome: A review of clinical, genetic, and endocrine findings","volume":"38","author":"Angulo","year":"2015","journal-title":"J. Endocrinol. Invest."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pmbts.2015.12.003","article-title":"Single gene and syndromic causes of obesity: Illustrative examples","volume":"140","author":"Butler","year":"2016","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1002\/ajmg.a.32249","article-title":"Array comparative genomic hybridization (aCGH) analysis in Prader-Willi syndrome","volume":"146A","author":"Butler","year":"2008","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4068","DOI":"10.3390\/ijms16024068","article-title":"The 15q11.2 BP1-BP2 microdeletion syndrome: A review","volume":"16","author":"Cox","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/jir.12382","article-title":"Clinical and genetic aspects of the 15q11.2 BP1-BP2 microdeletion disorder","volume":"61","author":"Butler","year":"2017","journal-title":"J. Intellect. Disabil. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1109","DOI":"10.1038\/tp.2017.77","article-title":"15q11.2 CNV affects cognitive, structural and functional correlates of dyslexia and dyscalculia","volume":"7","author":"Ulfarsson","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"ref_14","unstructured":"Davis, K.W., Serrano, M., Loddo, S., Robinson, C., Alesi, V., Dallapiccola, B., Novelli, A., and Butler, M.G. (2019). Parent-of-origin effects in 15q11.2 BP1-BP2 microdeletion (Burnside-Butler) syndrome. Int. J. Mol. Sci., 20."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00439-011-0970-4","article-title":"Microdeletion\/microduplication of proximal 15q11.2 between BP1 and BP2: A susceptibility region for neurological dysfunction including developmental and language delay","volume":"130","author":"Burnside","year":"2011","journal-title":"Hum. Genet."},{"key":"ref_16","first-page":"2846","article-title":"Genetic counseling for susceptibility loci and neurodevelopmental disorders: The del15q11.2 as an example","volume":"161A","author":"Brison","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/gim.2012.164","article-title":"Estimates of penetrance for recurrent pathogenic copy-number variations","volume":"15","author":"Rosenfeld","year":"2013","journal-title":"Genet. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/aur.1378","article-title":"Modest impact on risk for autism spectrum disorder of rare copy number variants at 15q11.2, specifically breakpoints 1 to 2","volume":"7","author":"Chaste","year":"2014","journal-title":"Autism Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1002\/ajmg.a.37134","article-title":"Deletion of 15q11.2(BP1-BP2) region: Further evidence for lack of phenotypic specificity in a pediatric population","volume":"67A","author":"Hashemi","year":"2015","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ho, K.S., Wassman, E.R., Baxter, A.L., Hensel, C.H., Martin, M.M., Prasad, A., Twede, H., Vanzo, R.J., and Butler, M.G. (2016). Chromosomal microarray analysis of consecutive individuals with Autism Spectrum Disorders using an ultra-high resolution chromosomal microarray optimized for neurodevelopmental disorders. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122070"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1086\/378817","article-title":"NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6)","volume":"73","author":"Rainier","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/humu.20126","article-title":"Distinct novel mutations affecting the same base in the NIPA1 gene cause autosomal dominant hereditary spastic paraplegia in two Chinese families","volume":"25","author":"Chen","year":"2005","journal-title":"Hum. Mutat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"234. e9","DOI":"10.1016\/j.neurobiolaging.2018.09.012","article-title":"Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort","volume":"74","author":"Tazelaar","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Xie, H., Zhang, Y., Zhang, P., Wang, J., Wu, Y., Wu, X., Netoff, T., and Jiang, Y. (2014). Functional study of NIPA2 mutations identified from the patients with childhood absence epilepsy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109749"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.2741\/2039","article-title":"Magnesium transporters: Properties, regulation and structure","volume":"11","author":"Maguire","year":"2006","journal-title":"Front. Biosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.eplepsyres.2012.02.004","article-title":"Can magnesium supplementation reduce seizures in people with epilepsy? A hypothesis","volume":"100","author":"Yuen","year":"2012","journal-title":"Epilepsy Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"C407","DOI":"10.1152\/ajpcell.00124.2009","article-title":"Molecular identification of ancient and modern mammalian magnesium transporters","volume":"298","author":"Quamme","year":"2010","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1113\/jphysiol.2004.080200","article-title":"A critical role of TRPM channel-kinase for human magnesium transport","volume":"566","author":"Schlingmann","year":"2005","journal-title":"J. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.mehy.2009.10.051","article-title":"Magnesium for treatment-resistant depression: A review and hypothesis","volume":"74","author":"Eby","year":"2010","journal-title":"Med. Hypotheses"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Vink, R., and Nechifor, M. (2011). Magnesium transport across the blood-brain barriers. Magnesium in the Central Nervous System, University of Adelaide Press.","DOI":"10.1017\/UPO9780987073051"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Liu, N.N., Xie, H., Xiang-Wei, W.S., Gao, K., Wang, T.S., and Jiang, Y.W. (2019). The absence of NIPA2 enhances neural excitability through BK (big potassium) channels. CNS Neurosci. Ther.","DOI":"10.1111\/cns.13119"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Dribben, W.H., Eisenman, L.N., and Mennerick, S. (2010). Magnesium induces neuronal apoptosis by suppressing excitability. Magnesium induces neuronal apoptosis by suppressing excitability. Cell Death Dis.","DOI":"10.1038\/cddis.2010.39"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7118","DOI":"10.1007\/s12035-018-0896-0","article-title":"Magnesium Reduces Blood-Brain Barrier Permeability and Regulates Amyloid-\u03b2 Transcytosis","volume":"55","author":"Zhu","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.lfs.2016.12.010","article-title":"Effects of MgSO4 and magnesium transporters on 6-hydroxydopamine-induced SH-SY5Y cells","volume":"172","author":"Lin","year":"2017","journal-title":"Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jpsychires.2019.01.021","article-title":"Microduplications at the 15q11.2 BP1-BP2 locus are enriched in patients with anorexia nervosa","volume":"113","author":"Chang","year":"2019","journal-title":"J. Psychiatr. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8060","DOI":"10.1074\/jbc.M610314200","article-title":"NIPA1 (SPG6), the basis for autosomal dominant form of hereditary spastic paraplegia, encodes a functional Mg2+ transporter","volume":"282","author":"Goytain","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17065","DOI":"10.1038\/nrdp.2017.65","article-title":"Fragile X syndrome","volume":"3","author":"Hagerman","year":"2017","journal-title":"Nat. Rev. Dis. Primers."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/12\/2914\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:58:29Z","timestamp":1760187509000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/12\/2914"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,14]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["ijms20122914"],"URL":"https:\/\/doi.org\/10.3390\/ijms20122914","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,14]]}}}