{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T23:57:10Z","timestamp":1774310230951,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We describe a family with two maternal half\u2010brothers both of whom presented with muscular dystrophy, autism spectrum disorder, developmental delay, and sensorineural hearing loss. The elder brother had onset of features at ~3\u2009months of age, followed by clinical confirmation of muscular dystrophy at 3\u2009years. Skeletal biopsy staining at 4.7\u2009years showed an absence of dystrophin protein which prompted extensive molecular testing over 4\u2009years that included gene panels, targeted single\u2010gene assays, arrays, and karyotyping, all of which failed to identify a clinically significant variant in the <jats:italic>DMD<\/jats:italic> gene. At 10\u2009years of age, clinical whole\u2010genome sequencing (cWGS) was performed, which revealed a novel hemizygous ~50.7\u2009Mb balanced pericentric inversion on chromosome X that disrupts the <jats:italic>DMD<\/jats:italic> gene in both siblings, consistent with the muscular dystrophy phenotype. This inversion also impacts the upstream regulatory region of <jats:italic>POU3F4<\/jats:italic>, structural rearrangements which are known to cause hearing loss. The unaffected mother is a heterozygous carrier for the pericentric inversion. This finding illustrates the ability of cWGS to detect a wide breadth of disease\u2010causing genomic variations including large genomic rearrangements.<\/jats:p>","DOI":"10.1002\/ajmg.a.63462","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T09:38:51Z","timestamp":1699263531000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genome sequencing detects a balanced pericentric inversion with breakpoints that impact the <scp><i>DMD<\/i><\/scp> and upstream region of <scp><i>POU3F4<\/i><\/scp> genes"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5113-5576","authenticated-orcid":false,"given":"Anjana","family":"Chandrasekhar","sequence":"first","affiliation":[{"name":"Illumina Inc  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry J.","family":"Mroczkowski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Tennessee Health Science Center and Le Bonheur Children's Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"Urraca","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Tennessee Health Science Center and Le Bonheur Children's Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Gross","sequence":"additional","affiliation":[{"name":"Illumina Inc  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krista","family":"Bluske","sequence":"additional","affiliation":[{"name":"Illumina Inc  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Thorpe","sequence":"additional","affiliation":[{"name":"Illumina Inc  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. Tanner","family":"Hagelstrom","sequence":"additional","affiliation":[{"name":"Natera Inc  Austin Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven A.","family":"Schonberg","sequence":"additional","affiliation":[{"name":"Quest Diagnostics  Chantilly Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise L.","family":"Perry","sequence":"additional","affiliation":[{"name":"Illumina Inc  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan J.","family":"Taft","sequence":"additional","affiliation":[{"name":"Illumina Inc  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akanchha","family":"Kesari","sequence":"additional","affiliation":[{"name":"Illumina Inc  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,11,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/CND.0000000000000436"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1044\/1059-0889(2013\/13-0018)"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv710"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-013-2386-3"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2023.100258"},{"key":"e_1_2_8_7_1","article-title":"Genome sequencing as a diagnostic test in children with unexplained medical complexity","volume":"3","author":"Costain G.","year":"2020","journal-title":"Journal of American Medical Association Network Open"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal5209"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7839145"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.9.1229"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm132"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a003392"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198805263182104"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22353"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.119"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01242-6"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(88)90113-9"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24191"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116402"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24106"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1996.03530410049032"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2014.54"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25983"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/AUD.0000000000001073"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10212"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24343"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.2028"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63462","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T09:56:11Z","timestamp":1707818171000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,6]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/ajmg.a.63462"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63462","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,6]]},"assertion":[{"value":"2023-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63462"}}