{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:05:17Z","timestamp":1792166717437,"version":"4.4.0"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2014,11,5]],"date-time":"2014-11-05T00:00:00Z","timestamp":1415145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nail patella syndrome (NPS) is an autosomal dominant disorder characterized by nail malformations, patellar apoplasia, or patellar hypoplasia. Mutations within the LMX1B gene are found in 85% of families with NPS; thus, this gene has been characterized as the causative gene of NPS. In this study, we identified a heterozygous microdeletion of the entire LMX1B gene using multiplex ligation-dependent probe amplification (MLPA) in a Chinese family with NPS. The determination of the deletion breakpoints by Illumina genome-wide DNA analysis beadchip showed that the deletion was located in chromosome 9q33.3 and spanned about 0.66 Mb in size. This heterozygous deletion provides strong evidence for haploinsufficiency as the pathogenic mechanism of NPS.     <\/jats:p>","DOI":"10.3390\/ijms151120158","type":"journal-article","created":{"date-parts":[[2014,11,6]],"date-time":"2014-11-06T02:48:56Z","timestamp":1415242136000},"page":"20158-20168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Microdeletion of Chromosome 9q33.3 Encompasses the Entire LMX1B Gene in a Chinese Family with Nail Patella Syndrome"],"prefix":"10.3390","volume":"15","author":[{"given":"Shujuan","family":"Jiang","sequence":"first","affiliation":[{"name":"Clinical Genetics, the Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiubin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Orthopedics Department, the First Affiliated Hospital, China Medical University,  Shenyang 110001, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Huang","sequence":"additional","affiliation":[{"name":"Clinical Genetics, the Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Genetics, the Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoliang","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Genetics, the Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinzhao","family":"Wang","sequence":"additional","affiliation":[{"name":"NO. 31 Middle School in Shenyang of Liaoning Province, Shenyang 110021, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"He","sequence":"additional","affiliation":[{"name":"Clinical Genetics, the Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Clinical Genetics, the Affiliated Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/j.1529-8817.2005.00191.x","article-title":"Nail patella syndrome revisited: 50 years after linkage","volume":"69","author":"McIntosh","year":"2005","journal-title":"Ann. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0140-6736(50)90636-2","article-title":"Renal dysplasia in a family with multiple hereditary abnormalities including iliac horns","volume":"1","author":"Hawkins","year":"1950","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1136\/bjo.2006.092619","article-title":"Nail patella syndrome and its association with glaucoma: A review of eight families","volume":"90","author":"Mimiwati","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_4","first-page":"639","article-title":"Novel LMX1B mutation in familial Nail patella syndrome with variable expression of open angle glaucoma","volume":"13","author":"Milla","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S82","DOI":"10.3346\/jkms.2009.24.S1.S82","article-title":"Clinico-genetic study of nail patella syndrome","volume":"24","author":"Lee","year":"2009","journal-title":"J. Korean Med. Sci."},{"key":"ref_6","first-page":"1929","article-title":"c.194 A>C (Q65P) mutation in the LMX1B gene in patients with nail patella syndrome associated with glaucoma","volume":"17","author":"Romero","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/ng0598-47","article-title":"Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome","volume":"19","author":"Dreyer","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/hmg\/7.7.1091","article-title":"Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail patella syndrome","volume":"7","author":"Vollrath","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1086\/302165","article-title":"Mutation analysis of LMX1B gene in nail patella syndrome patients","volume":"63","author":"McIntosh","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1006\/geno.1997.5075","article-title":"Identification of a human LMX1 (LMX1.1)-related gene, LMX1.2: Tissue-specific expression and linkage mapping on chromosome 9","volume":"46","author":"Iannotti","year":"1997","journal-title":"Genomics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/(SICI)1521-1878(199801)20:1<58::AID-BIES9>3.0.CO;2-O","article-title":"DeLIMiting development","volume":"20","author":"Curtiss","year":"1998","journal-title":"Bioessays"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e15998","DOI":"10.1371\/journal.pone.0015998","article-title":"Adult raphe-specific deletion of LMX1b leads to central serotonin deficiency","volume":"6","author":"Song","year":"2011","journal-title":"PLoS One"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/378716a0","article-title":"Dorsal cell fate specified by chick Lmx1 during vertebrate limb development","volume":"378","author":"Vogel","year":"1995","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1242\/dev.01250","article-title":"LMX1b controls the differentiation and migration of the superficial dorsal horn neurons of the spinal cord","volume":"131","author":"Ding","year":"2004","journal-title":"Development"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1172\/JCI0213961","article-title":"The LIM-homeodomain transcription factor LMX1b plays a crucial role in podocytes","volume":"109","author":"Rohr","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.mcn.2010.05.005","article-title":"The transcription factor, LMX1b, is necessary for the development of the principal trigeminal nucleus-based lemniscal pathway","volume":"44","author":"Xiang","year":"2010","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/ng0598-51","article-title":"Limb and kidney defects in LMX1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome","volume":"19","author":"Chen","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s11248-007-9118-7","article-title":"Renal phenotype in heterozygous LMX1b knockout mice (LMX1b+\/\u2212) after unilateral nephrectomy","volume":"16","author":"Endele","year":"2007","journal-title":"Transgen. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1136\/jmg.40.3.153","article-title":"Nail patella syndrome: A review of the phenotype aided by developmental biology","volume":"40","author":"Sweeney","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/(SICI)1098-1004(199912)14:6<459::AID-HUMU3>3.0.CO;2-9","article-title":"Restricted distribution of loss-of-function mutations within the LMX1B genes of nail patella syndrome patients","volume":"14","author":"Clough","year":"1999","journal-title":"Hum. Mutat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jdermsci.2008.04.014","article-title":"A novel LMX1B nonsense mutation in a family with nail patella syndrome","volume":"52","author":"Oshimo","year":"2008","journal-title":"J. Dermatol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1097\/GIM.0b013e3181e21afa","article-title":"A spectrum of LMX1B mutations in nail patella syndrome: New point mutations, deletion, and evidence of mosaicism in unaffected parents","volume":"12","author":"Marini","year":"2010","journal-title":"Genet. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"274","DOI":"10.3904\/kjim.2009.24.3.274","article-title":"A synonymous genetic alteration of LMX1B in a family with nail patella syndrome","volume":"24","author":"Ham","year":"2009","journal-title":"Korean J. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/sj.ejhg.5201446","article-title":"Genotype-phenotype studies in nail patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy","volume":"13","author":"Bongers","year":"2005","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1038\/ejhg.2008.83","article-title":"Identification of entire LMX1B gene deletions in nail patella syndrome: Evidence for haploinsufficiency as the main pathogenic mechanism underlying dominant inheritance in man","volume":"16","author":"Bongers","year":"2008","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_26","first-page":"285","article-title":"Identification of LMX1B gene point mutations in Italian patients affected with nail patella syndrome","volume":"4","author":"Seri","year":"1999","journal-title":"Int. J. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s00467-002-0911-5","article-title":"Nail patella syndrome. Overview on clinical and molecular findings","volume":"17","author":"Bongers","year":"2002","journal-title":"Pediatr. Nephrol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1681\/ASN.V1191762","article-title":"Nail patella syndrome: Identification of mutations in the LMX1B gene in Dutch families","volume":"11","author":"Knoers","year":"2000","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/humu.1217","article-title":"Twenty-two novel LMX1B mutations identified in nail patella syndrome (NPS) patients","volume":"18","author":"Hamlington","year":"2001","journal-title":"Hum. Mutat."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.bone.2008.04.025","article-title":"A novel mutation in LMX1B gene causes nail patella syndrome in a large Chinese family","volume":"43","author":"Lin","year":"2008","journal-title":"Bone"},{"key":"ref_31","unstructured":"UCSC Genome Browser on Human Feb. 2009 (GRCh37\/hg19) Assembly. Available online:http:\/\/genome.ucsc.edu."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1002\/ajmg.a.31685","article-title":"Ovotestes and XY sex reversal in a female with an interstitial 9q33.3\u2013q34.1 deletion encompassing NR5A1 and LMX1B causing features of Genitopatellar syndrome","volume":"143","author":"Schlaubitz","year":"2007","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/S0002-9394(14)70866-9","article-title":"Cosegregation of open-angle glaucoma and the nail patella syndrome","volume":"124","author":"Lichter","year":"1997","journal-title":"Am. J. Ophthalmol."},{"key":"ref_34","first-page":"59","article-title":"Increased symptoms of attention deficit hyperactivity disorder and major depressive disorder symptoms in nail patella syndrome: Potential association with LMX1B loss-of-function","volume":"156B","author":"Sparrow","year":"2011","journal-title":"Am. J. Med. Genet. B"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1203\/01.PDR.0000157674.63621.2C","article-title":"Functional characterization of LMX1B mutations associated with nail patella syndrome","volume":"57","author":"Sato","year":"2005","journal-title":"Pediatr. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/ndt\/gft359","article-title":"LMX1B mutation with residual transcriptional activity as a cause of isolated glomerulopathy","volume":"29","author":"Isojima","year":"2014","journal-title":"Nephrol. Dial. Transplant."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/15\/11\/20158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:08:56Z","timestamp":1760216936000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/15\/11\/20158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,5]]},"references-count":36,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2014,11]]}},"alternative-id":["ijms151120158"],"URL":"https:\/\/doi.org\/10.3390\/ijms151120158","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,5]]}}}