{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:19:43Z","timestamp":1778642383603,"version":"3.51.4"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,1,5]],"date-time":"2012-01-05T00:00:00Z","timestamp":1325721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The development of midbrain dopamine (DA) neurons is regulated by several transcription factors, including Nurr1, Wnt1, Lmx1a\/1b, En1, En2, Foxa1, Foxa2, and Pitx3. PITX3 is an upstream co\u2010activator of the <jats:italic>TH<\/jats:italic> (tyrosine hydroxylase) promoter. <jats:italic>Pitx3<\/jats:italic><jats:sup><jats:italic>\u2010\/\u2010<\/jats:italic><\/jats:sup> mice have a selective loss of dopaminergic neurons in the substantia nigra and ventral tegmental area, leading to the significantly reduced DA levels in the nigrostriatal pathway and in the dorsal striatum and manifest anomalous striatum\u2010dependent cognitive impairment and neurobehavioral activity. Treatment with <jats:sc>L<\/jats:sc>\u2010DOPA, dopamine, or dopamine receptor agonists in these mice reversed several of their sensorimotor impairments. Heterozygous missense mutations in <jats:italic>PITX3<\/jats:italic> have been reported in patients with autosomal dominant congenital cataract and anterior segment (ocular) mesenchymal dysgenesis (ASMD) whereas homozygous missense mutations have been found in patients with microphthalmia and neurological impairment. Using a clinical oligonucleotide array comparative genomic hybridization (aCGH), we have identified an \u223c317\u2009kb hemizygous deletion in 10q24.32, involving <jats:italic>PITX3<\/jats:italic> in a 17\u2010year\u2010old male with a Smith\u2013Magenis syndrome\u2010like phenotype, including mild intellectual impairment, sleep disturbance, hyperactivity, and aggressive and self\u2010destructive behavior. Interestingly, no eye anomalies were found in our patient. Analysis of neurotransmitters in his cerebrospinal fluid revealed an absence of <jats:sc>L<\/jats:sc>\u2010DOPA and significantly decreased levels of catecholamine metabolites. Importantly, <jats:sc>L<\/jats:sc>\u2010DOPA treatment of our patient has led to mild mitigation of his aggressive behavior and mild improvement of his attention span, extended time periods of concentration, and better sleep. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.32020","type":"journal-article","created":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T07:46:28Z","timestamp":1325835988000},"page":"236-242","source":"Crossref","is-referenced-by-count":17,"title":["Clinical improvement of the aggressive neurobehavioral phenotype in a patient with a deletion of <i>PITX3<\/i> and the absence of <scp>L<\/scp>\u2010DOPA in the cerebrospinal fluid"],"prefix":"10.1002","volume":"159B","author":[{"given":"Katarzyna","family":"Derwi\u0144ska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Mierzewska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicja","family":"Goszcza\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"El\u017cbieta","family":"Szczepanik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhilian","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Ku\u015bmierska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolanta","family":"Tryfon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kutkowska\u2010Ka\u017amierczak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Bocian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadeusz","family":"Mazurczak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Obersztyn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"Stankiewicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,1,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706128104"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.05.017"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.12.033"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002243"},{"key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00431-003-1161-7","article-title":"A new case of an interstitial deletion (4)(q25q27) characterised by molecular cytogenetic techniques and review of the literature","volume":"162","author":"Becker SA","year":"2003","journal-title":"Eur J Pediatr"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2008.117"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21947"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.03.008"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2010.05.032"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.020289"},{"key":"e_1_2_6_12_1","first-page":"1249","article-title":"A novel 1\u2010bp deletion in PITX3 causing congenital posterior polar cataract","volume":"17","author":"Berry V","year":"2011","journal-title":"Mol Vis"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31510"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm128"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1095"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2003.10.040"},{"key":"e_1_2_6_17_1","first-page":"367","article-title":"The PITX3 gene in posterior polar congenital cataract in Australia","volume":"12","author":"Burdon KP","year":"2006","journal-title":"Mol Vis"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.09.015"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2007.00879.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.08.014"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004270050243"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.031211"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960329)62:3<247::AID-AJMG9>3.0.CO;2-Q"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23693"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.10.004"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.02.015"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.12.1753"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3718-04.2005"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(03)00162-1"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06404.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.12.014"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.029769"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200963"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2007.08.032"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20540"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp043"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00257.x"},{"key":"e_1_2_6_38_1","first-page":"855","article-title":"The role of transcription factor Pitx3 in dopamine neuron development and Parkinson's disease","volume":"9","author":"Li J","year":"2009","journal-title":"Curr Top Med Chem"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.03.064"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511153103"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.03.028"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21924"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2006.11.003"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0230529100"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06784.x"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm241"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(01)00305-7"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101193108"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-009-9235-0"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-8-84"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/527"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.11.1575"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.083501.108"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(01)00254-1"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2004.11.012"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-004-0943-1"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.24.13305"},{"key":"e_1_2_6_58_1","first-page":"2010","article-title":"Anterior segment mesenchymal dysgenesis in a large Australian family is associated with the recurrent 17 bp duplication in PITX3","volume":"14","author":"Summers KM","year":"2008","journal-title":"Molec Vision"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.93"},{"key":"e_1_2_6_60_1","first-page":"100","volume-title":"Human chromosomes \u2013 manual of basic technologies","author":"Verma RS","year":"1998"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2010.03281.x"}],"container-title":["American Journal of Medical Genetics Part B: Neuropsychiatric Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.b.32020","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.b.32020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T12:12:59Z","timestamp":1697026379000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.b.32020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,5]]},"references-count":60,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,3]]}},"alternative-id":["10.1002\/ajmg.b.32020"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.b.32020","archive":["Portico"],"relation":{},"ISSN":["1552-4841","1552-485X"],"issn-type":[{"value":"1552-4841","type":"print"},{"value":"1552-485X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,5]]}}}