{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:31:21Z","timestamp":1790206281079,"version":"4.1.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000065","name":"U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS105078"],"award-info":[{"award-number":["NS105078"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Hum Genet"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite extensive research into the genetic underpinnings of neurodevelopmental disorders (NDD), many clinical cases remain unresolved. We studied a female proband with a NDD, mildly dysmorphic facial features, and brain stem hypoplasia on neuroimaging. Comprehensive genomic analyses revealed a terminal 5p loss and a\u00a0terminal 18q gain in the proband while a diploid copy number for chromosomes 5 and 18 in both parents. Genomic investigations in the proband identified an unbalanced translocation t(5;18) with additional genetic material from chromosome 2 (2q31.3) inserted at the breakpoint, pointing to a complex chromosomal rearrangement (CCR) involving 5p15.2, 2q31.3, and 18q21.32. Breakpoint junction analyses enabled by long-read genome sequencing unveiled the presence of four distinct junctions in the father, who is a\u00a0carrier of a balanced CCR. The proband inherited from the father both the abnormal chromosome 5 resulting in segmental aneusomies of chr5 (loss) and chr18 (gain) and a der(2) homologue. Evidences suggest a chromoplexy mechanism for this CCR derivation, involving double-strand breaks (DSBs) repaired by non-homologous end joining (NHEJ) or alternative end joining (alt-EJ). The complexity of the CCR and the segregation of homologues elucidate the genetic model for this family. This study demonstrates the importance of combining multiple genomic technologies to uncover genetic causes of complex neurodevelopmental syndromes and to better understand genetic disease mechanisms.<\/jats:p>","DOI":"10.1038\/s41431-024-01680-1","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T04:11:54Z","timestamp":1725941514000},"page":"231-238","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genomic Balancing Act: deciphering DNA rearrangements in the complex chromosomal aberration involving 5p15.2, 2q31.1, and 18q21.32"],"prefix":"10.1038","volume":"33","author":[{"given":"Zain","family":"Dardas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Marafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhi","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawid M.","family":"Fatih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnia F.","family":"El-Rashidy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Grochowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2090-298X","authenticated-orcid":false,"given":"Claudia M. B.","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini N.","family":"Jhangiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowei","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Gibbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-6765","authenticated-orcid":false,"given":"Jennifer E.","family":"Posey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6860-372X","authenticated-orcid":false,"given":"Daniel G.","family":"Calame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7840-0002","authenticated-orcid":false,"given":"Maha S.","family":"Zaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9907-9246","authenticated-orcid":false,"given":"James R.","family":"Lupski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,10]]},"reference":[{"key":"1680_CR1","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.tig.2009.05.005","volume":"25","author":"F Zhang","year":"2009","unstructured":"Zhang F, Carvalho CMB, Lupski JR. Complex human chromosomal and genomic rearrangements. Trends Genet. 2009;25:298.","journal-title":"Trends Genet"},{"key":"1680_CR2","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1093\/humupd\/dmr010","volume":"17","author":"F Pellestor","year":"2011","unstructured":"Pellestor F, Anahory T, Lefort G, Puechberty J, Liehr T, H\u00e9don B, et al. Complex chromosomal rearrangements: origin and meiotic behavior. Hum Reprod Update. 2011;17:476\u201394. https:\/\/doi.org\/10.1093\/humupd\/dmr010.","journal-title":"Hum Reprod Update"},{"key":"1680_CR3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/jcp.25048","volume":"231","author":"WJ Cannan","year":"2016","unstructured":"Cannan WJ, Pederson DS. Mechanisms and consequences of double-strand DNA break formation in chromatin. J Cell Physiol. 2016;231:3.","journal-title":"J Cell Physiol"},{"key":"1680_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13073-017-0412-6","volume":"9","author":"MK Eldomery","year":"2017","unstructured":"Eldomery MK, Coban-Akdemir Z, Harel T, Rosenfeld JA, Gambin T, Stray-Pedersen A, et al. Lessons learned from additional research analyses of unsolved clinical exome cases. Genome Med. 2017;9:1\u201315. https:\/\/genomemedicine.biomedcentral.com\/articles\/10.1186\/s13073-017-0412-6.","journal-title":"Genome Med"},{"key":"1680_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-13-8","volume":"13","author":"D Challis","year":"2012","unstructured":"Challis D, Yu J, Evani US, Jackson AR, Paithankar S, Coarfa C, et al. An integrative variant analysis suite for whole exome next-generation sequencing data. BMC Bioinform. 2012;13:1\u201312. https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-13-8.","journal-title":"BMC Bioinform"},{"key":"1680_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-15-30","volume":"15","author":"JG Reid","year":"2014","unstructured":"Reid JG, Carroll A, Veeraraghavan N, Dahdouli M, Sundquist A, English A, et al. Launching genomics into the cloud: Deployment of Mercury, a next generation sequence analysis pipeline. BMC Bioinform. 2014;15:1\u201311. https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-15-30.","journal-title":"BMC Bioinform"},{"key":"1680_CR7","doi-asserted-by":"publisher","unstructured":"Du H, Dardas Z, Jolly A, Grochowski CM, Jhangiani SN, Li H, et al. HMZDupFinder: a robust computational approach for detecting intragenic homozygous duplications from exome sequencing data. Nucleic Acids Res. 2023;28:gkad1223. https:\/\/doi.org\/10.1093\/nar\/gkad1223.","DOI":"10.1093\/nar\/gkad1223"},{"key":"1680_CR8","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.ajhg.2012.08.005","volume":"91","author":"M Fromer","year":"2012","unstructured":"Fromer M, Moran JL, Chambert K, Banks E, Bergen SE, Ruderfer DM, et al. Discovery and statistical genotyping of copy-number variation from whole-exome sequencing depth. Am J Hum Genet. 2012;91:597\u2013607. https:\/\/pubmed.ncbi.nlm.nih.gov\/23040492\/.","journal-title":"Am J Hum Genet"},{"key":"1680_CR9","doi-asserted-by":"publisher","first-page":"2188","DOI":"10.1093\/hmg\/ddp151","volume":"18","author":"CMB Carvalho","year":"2009","unstructured":"Carvalho CMB, Zhang F, Liu P, Patel A, Sahoo T, Bacino CA, et al. Complex rearrangements in patients with duplications of MECP2 can occur by fork stalling and template switching. Hum Mol Genet. 2009;18:2188\u2013203. https:\/\/pubmed.ncbi.nlm.nih.gov\/19324899\/.","journal-title":"Hum Mol Genet"},{"key":"1680_CR10","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1016\/j.ajhg.2021.08.009","volume":"108","author":"T Mitani","year":"2021","unstructured":"Mitani T, Isikay S, Gezdirici A, Gulec EY, Punetha J, Fatih JM, et al. High prevalence of multilocus pathogenic variation in neurodevelopmental disorders in the Turkish population. Am J Hum Genet. 2021;108:1981\u20132005.","journal-title":"Am J Hum Genet"},{"key":"1680_CR11","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1111\/dmcn.14722","volume":"63","author":"HF Lee","year":"2021","unstructured":"Lee HF, Chi CS, Tsai CR. Diagnostic yield and treatment impact of whole-genome sequencing in paediatric neurological disorders. Dev Med Child Neurol. 2021;63:934\u20138. https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.1111\/dmcn.14722.","journal-title":"Dev Med Child Neurol"},{"key":"1680_CR12","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1001\/jamapsychiatry.2016.3798","volume":"74","author":"MS Reuter","year":"2017","unstructured":"Reuter MS, Tawamie H, Buchert R, Gebril OH, Froukh T, Thiel C, et al. Diagnostic yield and novel candidate genes by exome sequencing in 152 consanguineous families with neurodevelopmental disorders. JAMA Psychiatry. 2017;74:293\u20139. https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/fullarticle\/2597704.","journal-title":"JAMA Psychiatry"},{"key":"1680_CR13","first-page":"1","volume":"24","author":"C Wang","year":"2023","unstructured":"Wang C, Zhou W, Zhang L, Fu L, Shi W, Qing Y, et al. Diagnostic yield and novel candidate genes for neurodevelopmental disorders by exome sequencing in an unselected cohort with microcephaly. BMC Genomics. 2023;24:1\u201314. https:\/\/bmcgenomics.biomedcentral.com\/articles\/10.1186\/s12864-023-09505-z.","journal-title":"BMC Genomics"},{"key":"1680_CR14","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/ng.564","volume":"42","author":"DF Conrad","year":"2010","unstructured":"Conrad DF, Bird C, Blackburne B, Lindsay S, Mamanova L, Lee C, et al. Mutation spectrum revealed by breakpoint sequencing of human germline CNVs. Nat Genet. 2010;42:385\u201391. https:\/\/www.nature.com\/articles\/ng.564.","journal-title":"Nat Genet"},{"key":"1680_CR15","doi-asserted-by":"crossref","unstructured":"Abel HJ, Larson DE, Regier AA, Chiang C, Das I, Kanchi KL, et al. Mapping and characterization of structural variation in 17,795 human genomes. Nature 2020;583:7814. https:\/\/www.nature.com\/articles\/s41586-020-2371-0.","DOI":"10.1038\/s41586-020-2371-0"},{"key":"1680_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13059-017-1158-6","volume":"18","author":"RL Collins","year":"2017","unstructured":"Collins RL, Brand H, Redin CE, Hanscom C, Antolik C, Stone MR, et al. Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome. Genome Biol. 2017;18:1\u201321. https:\/\/link.springer.com\/articles\/10.1186\/s13059-017-1158-6.","journal-title":"Genome Biol"},{"key":"1680_CR17","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/s00439-007-0359-6","volume":"121","author":"LELM Vissers","year":"2007","unstructured":"Vissers LELM, Stankiewicz P, Yatsenko SA, Crawford E, Creswick H, Proud VK, et al. Complex chromosome 17p rearrangements associated with low-copy repeats in two patients with congenital anomalies. Hum Genet. 2007;121:697\u2013709. https:\/\/pubmed.ncbi.nlm.nih.gov\/17457615\/.","journal-title":"Hum Genet"},{"key":"1680_CR18","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1007\/s00439-003-1079-1","volume":"114","author":"C Astbury","year":"2004","unstructured":"Astbury C, Christ LA, Aughton DJ, Cassidy SB, Fujimoto A, Pletcher BA, et al. Delineation of complex chromosomal rearrangements: evidence for increased complexity. Hum Genet. 2004;114:448\u201357. https:\/\/pubmed.ncbi.nlm.nih.gov\/14767757\/.","journal-title":"Hum Genet"},{"key":"1680_CR19","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.ajhg.2019.02.024","volume":"104","author":"CJ Zepeda-Mendoza","year":"2019","unstructured":"Zepeda-Mendoza CJ, Morton CC. The Iceberg under water: unexplored complexity of chromoanagenesis in congenital disorders. Am J Hum Genet. 2019;104:565\u201377.","journal-title":"Am J Hum Genet"},{"key":"1680_CR20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1002\/jcp.25053","volume":"231","author":"K Rodgers","year":"2016","unstructured":"Rodgers K, Mcvey M. Error-prone repair of DNA double-strand breaks. J Cell Physiol. 2016;231:15.","journal-title":"J Cell Physiol"},{"key":"1680_CR21","doi-asserted-by":"crossref","unstructured":"Pellestor F, Gaillard JB, Schneider A, Puechberty J, Gatinois V. Chromoanagenesis phenomena and their formation mechanisms. Cytogenomics. 2021;213\u201345.","DOI":"10.1016\/B978-0-12-823579-9.00009-6"},{"key":"1680_CR22","doi-asserted-by":"publisher","first-page":"708348","DOI":"10.3389\/fgene.2021.708348","volume":"12","author":"CM Grochowski","year":"2021","unstructured":"Grochowski CM, Krepischi ACV, Eisfeldt J, Du H, Bertola DR, Oliveira D, et al. Chromoanagenesis Event Underlies a de novo pericentric and multiple paracentric inversions in a single chromosome causing Coffin\u2013Siris Syndrome. Front Genet. 2021;12:708348.","journal-title":"Front Genet"},{"key":"1680_CR23","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/ng.3720","volume":"49","author":"C Redin","year":"2017","unstructured":"Redin C, Brand H, Collins RL, Kammin T, Mitchell E, Hodge JC, et al. The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies. Nat Genet. 2017;49:36\u201345. https:\/\/pubmed.ncbi.nlm.nih.gov\/27841880\/.","journal-title":"Nat Genet"},{"key":"1680_CR24","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.cell.2012.01.006","volume":"148","author":"CA Maher","year":"2012","unstructured":"Maher CA, Wilson RK. Chromothripsis and human disease: piecing together the shattering process. Cell. 2012;148:29\u201332. https:\/\/pubmed.ncbi.nlm.nih.gov\/22265399\/.","journal-title":"Cell"},{"key":"1680_CR25","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.tig.2022.03.001","volume":"38","author":"JR Lupski","year":"2022","unstructured":"Lupski JR. Biology in balance: human diploid genome integrity, gene dosage, and genomic medicine. Trends Genet. 2022;38:554.","journal-title":"Trends Genet."},{"key":"1680_CR26","doi-asserted-by":"crossref","unstructured":"Shen CH. Molecular diagnosis of gene mutation and inherited diseases. Diagn Mol Biol. 2023;425\u201355.","DOI":"10.1016\/B978-0-323-91788-9.00013-2"},{"key":"1680_CR27","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1750-1172-1-33","volume":"1","author":"P Cerruti Mainardi","year":"2006","unstructured":"Cerruti Mainardi P. Cri du Chat syndrome. Orphanet J Rare Dis. 2006;1:33\u201333. https:\/\/europepmc.org\/articles\/PMC1574300.","journal-title":"Orphanet J Rare Dis"},{"key":"1680_CR28","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/S0140-6736(60)90675-9","volume":"1","author":"JH Edwards","year":"1960","unstructured":"Edwards JH, Harnden DG, Cameron AH, Crosse VM, Wolf OH. A new trisomic syndrome. Lancet. 1960;1:787\u201390. https:\/\/pubmed.ncbi.nlm.nih.gov\/13819419\/.","journal-title":"Lancet"},{"key":"1680_CR29","doi-asserted-by":"crossref","unstructured":"Balasundaram P, Avulakunta ID. Edwards Syndrome. StatPearls; 2023. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK570597\/.","DOI":"10.1155\/2023\/5535083"},{"key":"1680_CR30","volume-title":"Smith\u2019s recognizable patterns of human malformation","author":"KL Jones","year":"2022","unstructured":"Jones KL, Jones MC. Smith\u2019s recognizable patterns of human malformation. 8th ed. Elsevier; 2022.","edition":"8th ed."},{"key":"1680_CR31","first-page":"1633","volume":"45","author":"T Gambin","year":"2017","unstructured":"Gambin T, Akdemir ZC, Yuan B, Gu S, Chiang T, Carvalho CMB, et al. Homozygous and hemizygous CNV detection from exome sequencing data in a Mendelian disease cohort. Nucleic Acids Res. 2017;45:1633\u201348. https:\/\/pubmed.ncbi.nlm.nih.gov\/27980096\/.","journal-title":"Nucleic Acids Res"},{"key":"1680_CR32","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/gim.2016.163","volume":"19","author":"R Pfundt","year":"2017","unstructured":"Pfundt R, Del Rosario M, Vissers LELM, Kwint MP, Janssen IM, De Leeuw N, et al. Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders. Genet Med. 2017;19:667\u201375. https:\/\/pubmed.ncbi.nlm.nih.gov\/28574513\/.","journal-title":"Genet Med"},{"key":"1680_CR33","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/s41431-023-01312-0","volume":"31","author":"M Pennings","year":"2023","unstructured":"Pennings M, Meijer RPP, Gerrits M, Janssen J, Pfundt R, de Leeuw N, et al. Copy number variants from 4800 exomes contribute to ~7% of genetic diagnoses in movement disorders, muscle disorders and neuropathies. Eur J Hum Genet. 2023;31:654\u201362. https:\/\/pubmed.ncbi.nlm.nih.gov\/36781956\/.","journal-title":"Eur J Hum Genet"},{"key":"1680_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.gimo.2024.101830","volume":"2","author":"Z Coban-Akdemir","year":"2024","unstructured":"Coban-Akdemir Z, Song X, Ceballos FC, Pehlivan D, Karaca E, Bayram Y, et al. The impact of the Turkish population variome on the genomic architecture of rare disease traits. Genet Med Open. 2024;2:101830. http:\/\/www.gimopen.org\/article\/S2949774424009762\/fulltext.","journal-title":"Genet Med Open"}],"container-title":["European Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41431-024-01680-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41431-024-01680-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41431-024-01680-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T14:06:52Z","timestamp":1739974012000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41431-024-01680-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,10]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["1680"],"URL":"https:\/\/doi.org\/10.1038\/s41431-024-01680-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3949622\/v1","asserted-by":"object"}]},"ISSN":["1018-4813","1476-5438"],"issn-type":[{"value":"1018-4813","type":"print"},{"value":"1476-5438","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,10]]},"assertion":[{"value":"11 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 May 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 August 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"JRL has stock ownership in 23andMe, is a paid consultant for Genome International, and is a co-inventor on multiple U.S. and European patents related to molecular diagnostics for inherited neuropathies, genomic disorders, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis and clinical genomic sequencing (both ES and GS) offered in the Baylor Genetics Laboratory (\n                      \n                      ). JRL serves on the Scientific Advisory Board of BG.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was approved by the institutional review board (IRB) at Baylor College of Medicine (BCM) (H-29697). Written informed consent was obtained from the families involved in this study in accordance with the Declaration of Helsinki. Written informed consent for publication of images was obtained.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}