{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:42:26Z","timestamp":1761745346191,"version":"build-2065373602"},"reference-count":17,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Italian Ministry of Health","award":["RC 08C723"],"award-info":[{"award-number":["RC 08C723"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Maternal uniparental disomy of chromosome 7 is present in 5\u201310% of patients with Silver-Russell syndrome (SRS), and duplication of 7p including GRB10 (Growth Factor Receptor-Bound Protein 10), an imprinted gene that affects pre-and postnatal growth retardation, has been associated with the SRS phenotype. Here, we report on a 17 year old girl referred to array-CGH analysis for short stature, psychomotor delay, and relative macrocephaly. Array-CGH analysis showed two copy number variants (CNVs): a ~12.7 Mb gain in 7p13-p11.2, involving GRB10 and an ~9 Mb loss in 7q11.21-q11.23. FISH experiments performed on the proband\u2019s mother showed a chromosome 7 pericentric inversion that might have mediated the complex rearrangement harbored by the daughter. Indeed, we found that segmental duplications, of which chromosome 7 is highly enriched, mapped at the breakpoints of both the mother\u2019s inversion and the daughter\u2019s CNVs. We postulate that pairing of highly homologous sequences might have perturbed the correct meiotic chromosome segregation, leading to unbalanced outcomes and acting as the putative meiotic mechanism that was causative of the proband\u2019s rearrangement. Comparison of the girl\u2019s phenotype to those of patients with similar CNVs supports the presence of 7p in a locus associated with features of SRS syndrome.<\/jats:p>","DOI":"10.3390\/ijms21228487","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T19:08:28Z","timestamp":1605121708000},"page":"8487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Recombinant Chromosome 7 Driven by Maternal Chromosome 7 Pericentric Inversion in a Girl with Features of Silver-Russell Syndrome"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8108-1521","authenticated-orcid":false,"given":"Ilaria","family":"Catusi","sequence":"first","affiliation":[{"name":"Laboratorio di Citogenetica e Genetica Molecolare, Istituto Auxologico Italiano, IRCCS, 20149 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"Bonati","sequence":"additional","affiliation":[{"name":"Ambulatorio di Genetica Medica, Istituto Auxologico Italiano, IRCCS, 20149 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ester","family":"Mainini","sequence":"additional","affiliation":[{"name":"Laboratorio di Citogenetica e Genetica Molecolare, Istituto Auxologico Italiano, IRCCS, 20149 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5893-0193","authenticated-orcid":false,"given":"Silvia","family":"Russo","sequence":"additional","affiliation":[{"name":"Laboratorio di Citogenetica e Genetica Molecolare, Istituto Auxologico Italiano, IRCCS, 20149 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Orlandini","sequence":"additional","affiliation":[{"name":"Ambulatorio di Genetica Medica, Istituto Auxologico Italiano, IRCCS, 20149 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1367-7227","authenticated-orcid":false,"given":"Lidia","family":"Larizza","sequence":"additional","affiliation":[{"name":"Laboratorio di Citogenetica e Genetica Molecolare, Istituto Auxologico Italiano, IRCCS, 20149 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-9837","authenticated-orcid":false,"given":"Maria Paola","family":"Recalcati","sequence":"additional","affiliation":[{"name":"Laboratorio di Citogenetica e Genetica Molecolare, Istituto Auxologico Italiano, IRCCS, 20149 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nrendo.2016.138","article-title":"Diagnosis and management of Silver\u2013Russell syndrome: First international consensus statement","volume":"13","author":"Wakeling","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1086\/302717","article-title":"Duplication of 7p11.2-p13, Including GRB10, in Silver-Russell Syndrome","volume":"66","author":"Monk","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_3","first-page":"376","article-title":"Chromosome 7p disruptions in Silver Russell syndrome: Delineating an imprinted candidate gene region","volume":"111","author":"Monk","year":"2002","journal-title":"Qual. Life Res."},{"key":"ref_4","first-page":"273","article-title":"Duplication of 7p12.1-p13, including GRB10 and IGFBP1, in a mother and daughter with features of Silver-Russell syndrome","volume":"105","author":"Joyce","year":"1999","journal-title":"Qual. Life Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1002\/ajmg.a.35612","article-title":"Heterogeneous growth patterns in carriers of chromosome 7p12.2 imbalances affecting GRB10","volume":"158A","author":"Eggermann","year":"2012","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_6","unstructured":"(2020, October 31). DECIPHER Database (DatabasE of genomiC varIation and Phenotype in Humans Using Ensembl Resources). Available online: https:\/\/decipher.sanger.ac.uk\/."},{"key":"ref_7","unstructured":"(2020, September 22). Online Mendelian Inheritance in Men (OMIM). Available online: omim.org."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103671","DOI":"10.1016\/j.ejmg.2019.103671","article-title":"Contribution of GRB10 to the prenatal phenotype in Silver-Russell syndrome? Lessons from 7p12 copy number variations","volume":"62","author":"Eggermann","year":"2019","journal-title":"Eur. J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1093\/hmg\/ddg110","article-title":"Conserved methylation imprints in the human and mouse GRB10 genes with divergent allelic expression suggests differential reading of the same mark","volume":"12","author":"Arnaud","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1136\/jmedgenet-2015-103601","article-title":"A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype","volume":"53","author":"Beunders","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1101\/gr.201160.115","article-title":"Characterizing polymorphic inversions in human genomes by single-cell sequencing","volume":"26","author":"Sanders","year":"2016","journal-title":"Genome Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1101\/gr.234831.118","article-title":"Inversion variants in human and primate genomes","volume":"28","author":"Catacchio","year":"2018","journal-title":"Genome Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1159\/000086903","article-title":"Sperm studies in heterozygote inversion carriers: A review","volume":"111","author":"Anton","year":"2005","journal-title":"Cytogenet. Genome Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.fertnstert.2005.09.023","article-title":"Genetic reproductive risk in inversion carriers","volume":"85","author":"Anton","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1093\/humrep\/del317","article-title":"Meiotic segregation analysis in spermatozoa of pericentric inversion carriers using fluorescence in-situ hybridization","volume":"22","author":"Morel","year":"2007","journal-title":"Hum. Reprod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"367","DOI":"10.3109\/19396368.2014.948580","article-title":"Different segregation patterns in five carriers due to a pericentric inversion of chromosome 1","volume":"60","author":"Luo","year":"2014","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_17","first-page":"214","article-title":"Segregation analysis in a man heterozygous for a pericentric inversion of chromosome 7 (p13;q36) by sperm chromosome studies","volume":"53","author":"Navarro","year":"1993","journal-title":"Am. J. Hum. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/22\/8487\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:32:09Z","timestamp":1760178729000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/22\/8487"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,11]]},"references-count":17,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ijms21228487"],"URL":"https:\/\/doi.org\/10.3390\/ijms21228487","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2020,11,11]]}}}