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The analysis of the shortest region of overlap (SRO) between deletions in\u2009~\u200940 patients has led to the identification of two critical regions and four strongly candidate genes (<jats:italic>BCL11A, REL, USP34<\/jats:italic> and <jats:italic>XPO1<\/jats:italic>). However, the delineation of their role in the occurrence of specific traits is hampered by their incomplete penetrance.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>To better delineate the role of hemizygosity of specific regions in selected traits by leveraging information both from penetrant and non\u2009\u2212\u2009penetrant deletions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Deletions in patients that do not present a specific trait cannot contribute to delineate the SROs. We recently developed a probabilistic model that, by considering also the non\u2009\u2212\u2009penetrant deletions, allows a more reliable assignment of peculiar traits to specific genomic segments. We apply this method adding two new patients to the published cases.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Our results delineate an intricate pattern of genotype\u2009\u2212\u2009phenotype correlation where <jats:italic>BCL11A<\/jats:italic> emerges as the main gene for autistic behavior while <jats:italic>USP34<\/jats:italic> and\/or <jats:italic>XPO1<\/jats:italic> haploinsufficiency are mainly associated with microcephaly, hearing loss and IUGR. <jats:italic>BCL11A, USP34<\/jats:italic> and <jats:italic>XPO1<\/jats:italic> genes are broadly related with brain malformations albeit with distinct patterns of brain damage.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The observed penetrance of deletions encompassing different SROs and that predicted when considering each single SRO as acting independently, may reflect a more complex model than the additive one. Our approach may improve the genotype\/phenotype correlation and may help to identify specific pathogenic mechanisms in contiguous gene syndromes.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s13258-023-01369-7","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T16:43:49Z","timestamp":1677170629000},"page":"491-505","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Trait\u2009\u2212\u2009driven analysis of the 2p15p16.1 microdeletion syndrome suggests a complex pattern of interactions between candidate genes"],"prefix":"10.1007","volume":"45","author":[{"given":"Martina","family":"Miceli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinella","family":"Failla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Saccuzzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ornella","family":"Galesi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvestra","family":"Amata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1049-0683","authenticated-orcid":false,"given":"Corrado","family":"Romano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7121-7712","authenticated-orcid":false,"given":"Maria Clara","family":"Bonaglia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8225-6880","authenticated-orcid":false,"given":"Marco","family":"Fichera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"key":"1369_CR1","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1101\/GR.184325.114","volume":"25","author":"T Andrews","year":"2015","unstructured":"Andrews T, Honti F, Pfundt R, de Leeuw N, Hehir\u2212Kwa J, van Silfhout AV, de Vries B, Webber C (2015) The clustering of functionally related genes contributes to CNV\u2212mediated disease. 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