{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T18:02:35Z","timestamp":1763748155768,"version":"3.37.3"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Interstitial 4q deletions are rare chromosomal alterations. Most of the previously reported deletions involving the 4q13.3 region are large chromosomal alterations with a common loss of band 4q21 resulting in marked growth restriction, severe intellectual disability, and absent or severely delayed speech. A microdeletion of 4q13.3 hasn\u2019t been previously reported. We discuss the involvement of genes and the observed phenotype, comparing it with that of previously reported patients.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>We report on a 4q13.3 microdeletion detected in three affected individuals of a Lithuanian family. The clinical features of two affected children and their affected mother are very similar and include short stature, congenital heart defect, skeletal anomalies, minor facial anomalies, delayed puberty, and intellectual disability. Whole genome SNP microarray analysis of one child revealed an interstitial 4q13.3 microdeletion, 1.56\u2009Mb in size. FISH analysis confirmed the deletion in the proband and identified the same deletion in her affected sib and mother, while it was not detected in a healthy sib. Deletion includes <jats:italic>ADAMTS3<\/jats:italic>, <jats:italic>ANKRD1<\/jats:italic>7, <jats:italic>COX18<\/jats:italic>, <jats:italic>GC<\/jats:italic>, and <jats:italic>NPFFR2<\/jats:italic> protein-coding genes.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our findings suggest that 4q13.3 microdeletion is a cause of a recognizable phenotype of three affected individuals. The detected microdeletion is the smallest interstitial deletion in 4q13. We highlight <jats:italic>ADAMTS3<\/jats:italic>, <jats:italic>ANKRD17<\/jats:italic> and <jats:italic>RNU4ATAC9P<\/jats:italic> as candidate genes for intellectual disability, growth retardation and congenital heart defect.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12920-020-0711-4","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T09:03:39Z","timestamp":1587027819000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A case report of familial 4q13.3 microdeletion in three individuals with syndromic intellectual disability"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8878-1259","authenticated-orcid":false,"given":"\u017divil\u0117","family":"Mald\u017eien\u0117","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelina M.","family":"Vait\u0117nien\u0117","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beata","family":"Aleksi\u016bnien\u0117","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Algirdas","family":"Utkus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Egl\u0117","family":"Preik\u0161aitien\u0117","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"issue":"2","key":"711_CR1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s13353-014-0197-x","volume":"55","author":"E Preiksaitiene","year":"2014","unstructured":"Preiksaitiene E, Molyt\u0117 A, Kasnauskiene J, Ciuladaite Z, Utkus A, Patsalis PC, Ku\u010dinskas V. Considering specific clinical features as evidence of pathogenic copy number variants. J Appl Genet. 2014;55(2):189\u201396.","journal-title":"J Appl Genet"},{"issue":"5","key":"711_CR2","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1136\/jmg.2009.072942","volume":"47","author":"LELM Vissers","year":"2010","unstructured":"Vissers LELM, de Vries BBA, Veltman JA. Genomic microarrays in mental retardation: from copy number variation to gene, from research to diagnosis. J Med Genet. 2010;47(5):289.","journal-title":"J Med Genet"},{"key":"711_CR3","doi-asserted-by":"crossref","unstructured":"Zollino M, Murdolo M, Marangi G, Pecile V, Galasso C, Mazzanti L, Neri G. On the nosology and pathogenesis of Wolf\u2013Hirschhorn syndrome: genotype\u2013phenotype correlation analysis of 80 patients and literature review. In: American Journal of Medical Genetics Part C: Seminars in Medical Genetics: 2008: Wiley Online Library; 2008. p. 257\u201369. https:\/\/onlinelibrary.wiley.com\/doi\/abs\/10.1002\/ajmg.c.30190.","DOI":"10.1002\/ajmg.c.30190"},{"issue":"6","key":"711_CR4","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1136\/jmg.2009.071902","volume":"47","author":"C Bonnet","year":"2010","unstructured":"Bonnet C, Andrieux J, B\u00e9ri-Dexheimer M, Leheup B, Boute O, Manouvrier S, Delobel B, Copin H, Receveur A, Mathieu M, et al. Microdeletion at chromosome 4q21 defines a new emerging syndrome with marked growth restriction, mental retardation and absent or severely delayed speech. J Med Genet. 2010;47(6):377.","journal-title":"J Med Genet"},{"issue":"1","key":"711_CR5","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1002\/ajmg.a.36821","volume":"167","author":"P Hemati","year":"2015","unstructured":"Hemati P, du Souich C, Boerkoel CF. 4q12\u20134q21. 21 deletion genotype\u2013phenotype correlation and the absence of piebaldism in presence of KIT haploinsufficiency. Am J Med Genet A. 2015;167(1):231\u20137.","journal-title":"Am J Med Genet A"},{"issue":"4","key":"711_CR6","first-page":"353","volume":"22","author":"BS Lipska","year":"2011","unstructured":"Lipska BS, Brzeskwiniewicz M, Wierzba J, Morzuchi L, Piotrowski A, Limon J. 8.6Mb interstitial deletion of chromosome 4q13.3q21.23 in a boy with cognitive impairment, short stature, hearing loss, skeletal abnormalities and facial dysmorphism. Genet Couns. 2011;22(4):353\u201363.","journal-title":"Genet Couns"},{"issue":"4","key":"711_CR7","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1002\/(SICI)1096-8628(19970414)69:4<400::AID-AJMG12>3.0.CO;2-R","volume":"69","author":"MJ Nowaczyk","year":"1997","unstructured":"Nowaczyk MJ, Teshima IE, Siegel-Bartelt J, Clarke JT. Deletion 4q21\/4q22 syndrome: two patients with de novo 4q21.3q23 and 4q13.2q23 deletions. Am J Med Genet. 1997;69(4):400\u20135.","journal-title":"Am J Med Genet"},{"issue":"12","key":"711_CR8","doi-asserted-by":"publisher","first-page":"3113","DOI":"10.1002\/ajmg.a.37291","volume":"167","author":"I Quintela","year":"2015","unstructured":"Quintela I, Barros F, Fernandez-Prieto M, Martinez-Regueiro R, Castro-Gago M, Carracedo A, Gomez-Lado C, Eiris J. Interstitial microdeletions including the chromosome band 4q13. 2 and the UBA6 gene as possible causes of intellectual disability and behavior disorder. Am J Med Genet A. 2015;167(12):3113\u201320.","journal-title":"Am J Med Genet A"},{"issue":"8","key":"711_CR9","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1002\/ajmg.a.36027","volume":"161","author":"S Shimada","year":"2013","unstructured":"Shimada S, Okamoto N, Nomura S, Fukui M, Shimakawa S, Sangu N, Shimojima K, Osawa M, Yamamoto T. Microdeletions of 5.5 Mb (4q13. 2\u2013q13. 3) and 4.1 Mb (7p15. 3\u2013p21. 1) associated with a saethre\u2013chotzen-like phenotype, severe intellectual disability, and autism. Am J Med Genet A. 2013;161(8):2078\u201383.","journal-title":"Am J Med Genet A"},{"key":"711_CR10","volume-title":"The Wechsler adult intelligence scale\u2014fourth edition and the Wechsler memory scale\u2014fourth edition","author":"LW Drozdick","year":"2012","unstructured":"Drozdick LW, Wahlstrom D, Zhu J, Weiss LG. The Wechsler adult intelligence scale\u2014fourth edition and the Wechsler memory scale\u2014fourth edition; 2012."},{"key":"711_CR11","volume-title":"Assessment of children's intelligence: Saunders Philadelphia","author":"JM Sattler","year":"1974","unstructured":"Sattler JM. Assessment of children's intelligence: Saunders Philadelphia; 1974."},{"key":"711_CR12","volume-title":"Diagnostic cytogenetics: Springer Science & Business Media","author":"R-D Wegner","year":"2013","unstructured":"Wegner R-D. Diagnostic cytogenetics: Springer Science & Business Media; 2013."},{"issue":"1","key":"711_CR13","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1159\/000486947","volume":"154","author":"B Aleksi\u016bnien\u0117","year":"2018","unstructured":"Aleksi\u016bnien\u0117 B, Preiksaitiene E, Mork\u016bnien\u0117 A, Ambrozaityt\u0117 L, Utkus A. A de novo 1q22q23.1 interstitial microdeletion in a girl with intellectual disability and multiple congenital anomalies including congenital heart defect. Cytogen Genome Res. 2018;154(1):6\u201311.","journal-title":"Cytogen Genome Res"},{"issue":"4","key":"711_CR14","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.ajhg.2009.03.010","volume":"84","author":"HV Firth","year":"2009","unstructured":"Firth HV, Richards SM, Bevan AP, Clayton S, Corpas M, Rajan D, Van Vooren S, Moreau Y, Pettett RM, Carter NP. DECIPHER: database of chromosomal imbalance and phenotype in humans using Ensembl resources. Am J Hum Genet. 2009;84(4):524\u201333.","journal-title":"Am J Hum Genet"},{"issue":"46","key":"711_CR15","doi-asserted-by":"publisher","first-page":"31493","DOI":"10.1074\/jbc.R109.052340","volume":"284","author":"SS Apte","year":"2009","unstructured":"Apte SS. A Disintegrin-like and Metalloprotease (Reprolysin-type) with Thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms. J Biol Chem. 2009;284(46):31493\u20137.","journal-title":"J Biol Chem"},{"issue":"8","key":"711_CR16","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1242\/dev.02308","volume":"133","author":"C Le Goff","year":"2006","unstructured":"Le Goff C, Somerville RP, Kesteloot F, Powell K, Birk DE, Colige AC, Apte SS. Regulation of procollagen amino-propeptide processing during mouse embryogenesis by specialization of homologous ADAMTS proteases: insights on collagen biosynthesis and dermatosparaxis. Development. 2006;133(8):1587\u201396.","journal-title":"Development"},{"issue":"17","key":"711_CR17","doi-asserted-by":"publisher","first-page":"2765","DOI":"10.1016\/j.febslet.2009.07.025","volume":"583","author":"S-C Hou","year":"2009","unstructured":"Hou S-C, Chan L-W, Chou Y-C, Su C-Y, Chen X, Shih Y-L, Tsai P-C, Shen CKJ, Yan Y-T. Ankrd17, an ubiquitously expressed ankyrin factor, is essential for the vascular integrity during embryogenesis. FEBS Lett. 2009;583(17):2765\u201371.","journal-title":"FEBS Lett"},{"issue":"12","key":"711_CR18","doi-asserted-by":"publisher","first-page":"7875","DOI":"10.1074\/jbc.M807827200","volume":"284","author":"M Deng","year":"2009","unstructured":"Deng M, Li F, Ballif BA, Li S, Chen X, Guo L, Ye X. Identification and functional analysis of a novel Cyclin E\/Cdk2 substrate Ankrd17. J Biol Chem. 2009;284(12):7875\u201388.","journal-title":"J Biol Chem"},{"issue":"1","key":"711_CR19","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1111\/jcmm.12952","volume":"21","author":"Y An","year":"2017","unstructured":"An Y, Furber KL, Ji S. Pseudogenes regulate parental gene expression via ce RNA network. J Cell Mol Med. 2017;21(1):185\u201392.","journal-title":"J Cell Mol Med"},{"key":"711_CR20","doi-asserted-by":"publisher","first-page":"8718","DOI":"10.1038\/ncomms9718","volume":"6","author":"D Merico","year":"2015","unstructured":"Merico D, Roifman M, Braunschweig U, Yuen RKC, Alexandrova R, Bates A, Reid B, Nalpathamkalam T, Wang Z, Thiruvahindrapuram B, et al. Compound heterozygous mutations in the noncoding RNU4ATAC cause Roifman syndrome by disrupting minor intron splicing. Nat Commun. 2015;6:8718.","journal-title":"Nat Commun"}],"container-title":["BMC Medical Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-020-0711-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12920-020-0711-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-020-0711-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T01:18:56Z","timestamp":1618535936000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedgenomics.biomedcentral.com\/articles\/10.1186\/s12920-020-0711-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,16]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["711"],"URL":"https:\/\/doi.org\/10.1186\/s12920-020-0711-4","relation":{},"ISSN":["1755-8794"],"issn-type":[{"type":"electronic","value":"1755-8794"}],"subject":[],"published":{"date-parts":[[2020,4,16]]},"assertion":[{"value":"6 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Written informed consents were obtained from the participants and the parents of the child for genetic investigation. The study was approved by the Vilnius Regional Biomedical Research Ethics Committee of Lithuania.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The family provided the consent for the case report to be published. Written informed consents regarding photographs for publication have been obtained from the participant and the parents of the child.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declared no potential conflicts of interest with respect to the research, authorship, and\/or publication of this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"63"}}