A de novo 2.2 Mb recurrent 17q23.1q23.2 deletion unmasks novel putative regulatory non-coding SNVs associated with lethal lung hypoplasia and pulmonary hypertension: A case report
Authors:
- Justyna A. Karolak,
- Tomasz Gambin,
- Engela M. Honey,
- Tomas Slavik,
- Edwina Popek,
- P. Stankiewicz
Abstract
Background: Application of whole genome sequencing (WGS) enables identification of non-coding variants that play a phenotype-modifying role and are undetectable by exome sequencing. 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. Case presentation: 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, two heterozygous recurrent CNV deletions: ~ 2.2 Mb on 17q23.1q23.2, involving TBX4, and ~ 600 kb on 16p11.2, involving TBX6, that both arose de novo on maternal chromosomes were identified. In the predicted lung-specific enhancer upstream to TBX4, 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. Conclusions: Our findings further support a recently reported model of complex compound inheritance of LLDD in which both non-coding and coding heterozygous TBX4 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.
- Record ID
- WUT8e3c61371fea4509b93b663099c33218
- Author
- Journal series
- BMC Medical Genomics, ISSN 1755-8794
- Issue year
- 2020
- Vol
- 13
- ASJC Classification
- ;
- DOI
- DOI:10.1186/s12920-020-0701-6 Opening in a new tab
- Language
- (en) English
- Score (nominal)
- 100
- Score source
- journalList
- Score
- = 100.0, 09-05-2022, ArticleFromJournal
- Publication indicators
- = 5; = 0; : 2018 = 0.922; : 2018 (2 years) = 2.568 - 2018 (5 years) =3.062
- Uniform Resource Identifier
- https://repo.pw.edu.pl/info/article/WUT8e3c61371fea4509b93b663099c33218/
- URN
urn:pw-repo:WUT8e3c61371fea4509b93b663099c33218
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or PerishOpening in a new tab system.