{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:21:29Z","timestamp":1747146089566,"version":"3.40.5"},"reference-count":13,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T00:00:00Z","timestamp":1574640000000},"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 C"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We describe an overgrowth condition associated with X\u2010linked copy number variation. Three brothers displayed an overgrowth pattern at birth that continued postnatally. Clinical findings included macrocephaly, distinctive facial features, developmental delay and variable clubfoot. Normal fetal growth was noted until the third trimester by Hadlock standards, revealing a late gestational overgrowth pattern. Microarray analysis in the family showed a maternally inherited 680\u2009kb copy number duplication at Xq26.1\u2010q26.2 in all three brothers. Molecular sequencing for known overgrowth conditions including <jats:italic>GPC3<\/jats:italic>, Sotos 1 (<jats:italic>NSD1<\/jats:italic>), Malan (<jats:italic>NFIX<\/jats:italic>), Perlman (<jats:italic>DIS3L2<\/jats:italic>), Weaver (<jats:italic>EZH2<\/jats:italic>), Opitz\u2013Kaveggia (<jats:italic>MED12<\/jats:italic>) loci were negative. BWS IC1 and IC2 methylation and <jats:italic>CDKN1C<\/jats:italic> testing was also negative. Normal IGF1 levels excluded X\u2010linked acrogiantism. The duplicated region Xq26.1\u2010q26.2 contained <jats:italic>IGSF1<\/jats:italic> and at least part of the lncRNA <jats:italic>FIRRE<\/jats:italic>. <jats:italic>IGSF1<\/jats:italic>, a highly expressed pituitary immunoglobulin superfamily gene, was recently implicated in a genome\u2010wide association study of canine size. <jats:italic>IGSF1<\/jats:italic> variants were associated with large canine breeds compared to smaller breeds. Our findings support the hypothesis that an X\u2010linked variant encompassing the <jats:italic>IGSF1<\/jats:italic> region may be associated with body size. Although <jats:italic>IGSF1<\/jats:italic> loss has been noted in human hypothyroidism, this is the first reported phenotype in a family with copy number duplication in the region. Our findings suggest that prenatal evaluation, cross\u2010species evaluation, Mendelian, and GWAS studies may describe a distinctive familial condition and its corresponding phenotypic features.<\/jats:p>","DOI":"10.1002\/ajmg.c.31756","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T09:20:22Z","timestamp":1574673622000},"page":"644-649","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["X\u2010linked duplication copy number variation in a familial overgrowth condition"],"prefix":"10.1002","volume":"181","author":[{"given":"Thoa K.","family":"Ha","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics University of California San Francisco  San Francisco California"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences University of California San Francisco  San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne H.","family":"Mardy","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics University of California San Francisco  San Francisco California"},{"name":"Alameda Health System, Eastmont Wellness Center, Oakland, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniah","family":"Beleford","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics University of California San Francisco  San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Spanier","sequence":"additional","affiliation":[{"name":"Alameda Health System, Eastmont Wellness Center, Oakland, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brette V.","family":"Wayman","sequence":"additional","affiliation":[{"name":"UCSF Health Center for Clinical Genetics and Genomics University of California San Francisco  San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Penon\u2010Portmann","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics University of California San Francisco  San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun P.","family":"Wiita","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine University of California San Francisco  San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0746-6084","authenticated-orcid":false,"given":"Joseph T.","family":"Shieh","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics University of California San Francisco  San Francisco California"},{"name":"Institute for Human Genetics University of California San Francisco  San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,11,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00291401"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4613-0785-3_4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320170128"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-0710"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3182217a3a"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0396-241"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006661"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31800"},{"issue":"2","key":"e_1_2_7_10_1","first-page":"18","article-title":"A previously unrecognized X\u2010linked syndrome of dysmorphia","author":"Simpson J. 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