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Recently, non-coding regulatory single nucleotide variants (SNVs) have been reported in patients with lethal lung developmental disorders (LLDDs) or congenital scoliosis with recurrent copy-number variant (CNV) deletions at 17q23.1q23.2 or 16p11.2, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>Here, we report a deceased newborn with pulmonary hypertension and pulmonary interstitial emphysema with features suggestive of pulmonary hypoplasia, resulting in respiratory failure and neonatal death soon after birth. Using the array comparative genomic hybridization and WGS<jats:italic>,<\/jats:italic>two heterozygous recurrent CNV deletions: ~\u20092.2\u2009Mb on 17q23.1q23.2, involving<jats:italic>TBX4<\/jats:italic>, and ~\u2009600\u2009kb on 16p11.2, involving<jats:italic>TBX6,<\/jats:italic>that both arose de novo on maternal chromosomes were identified. In the predicted lung-specific enhancer upstream to<jats:italic>TBX4<\/jats:italic>, we have detected seven novel putative regulatory non-coding SNVs that were absent in 13 control individuals with the overlapping deletions but without any structural lung anomalies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings further support a recently reported model of complex compound inheritance of LLDD in which both non-coding and coding heterozygous<jats:italic>TBX4<\/jats:italic>variants contribute to the lung phenotype. In addition, this is the first report of a patient with combined de novo heterozygous recurrent 17q23.1q23.2 and 16p11.2 CNV deletions.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12920-020-0701-6","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T18:02:57Z","timestamp":1583517777000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A de novo 2.2\u2009Mb recurrent 17q23.1q23.2 deletion unmasks novel putative regulatory non-coding SNVs associated with lethal lung hypoplasia and pulmonary hypertension: a case report"],"prefix":"10.1186","volume":"13","author":[{"given":"Justyna A.","family":"Karolak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Gambin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engela M.","family":"Honey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Slavik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwina","family":"Popek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6456-7490","authenticated-orcid":false,"given":"Pawe\u0142","family":"Stankiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,6]]},"reference":[{"issue":"2","key":"701_CR1","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/S0168-9525(02)02592-1","volume":"18","author":"P Stankiewicz","year":"2002","unstructured":"Stankiewicz P, Lupski JR. 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In compliance with the Declaration of Helsinki, informed written consent for genetic study was obtained for participated individuals.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written consent for research study was obtained from the parents for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"34"}}