@article {576,
	title = {Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway.},
	journal = {Am J Hum Genet},
	volume = {104},
	year = {2019},
	month = {2019 02 07},
	pages = {213-228},
	abstract = {<p>Primary defects in lung branching morphogenesis, resulting in neonatal lethal pulmonary hypoplasias, are incompletely understood. To elucidate the pathogenetics of human lung development, we studied a unique collection of samples obtained from deceased individuals with clinically and histopathologically diagnosed interstitial neonatal lung disorders: acinar dysplasia (n = 14), congenital alveolar dysplasia (n = 2), and other lethal lung hypoplasias (n = 10). We identified rare heterozygous copy-number variant deletions or single-nucleotide variants (SNVs) involving TBX4 (n = 8 and n = 2, respectively) or FGF10 (n = 2 and n = 2, respectively) in 16/26 (61\%) individuals. In addition to TBX4, the overlapping \~{}2 Mb recurrent and nonrecurrent deletions at 17q23.1q23.2 identified in seven individuals with lung hypoplasia also remove a lung-specific enhancer region. Individuals with coding variants involving either TBX4 or FGF10 also harbored at least one non-coding SNV in the predicted lung-specific enhancer region, which was absent in 13 control individuals with the overlapping deletions but without any structural lung anomalies. The occurrence of rare coding variants involving TBX4 or FGF10 with the putative hypomorphic non-coding SNVs implies a complex compound inheritance of these pulmonary hypoplasias. Moreover, they support the importance of TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in human lung organogenesis and help to explain the histopathological continuum observed in these rare lethal developmental disorders of the lung.</p>},
	keywords = {DNA Copy Number Variations, Female, Fibroblast Growth Factor 10, Gene Expression Regulation, Gestational Age, Humans, Infant, Newborn, Infant, Newborn, Diseases, Lung, Lung Diseases, Male, Maternal Inheritance, Organogenesis, Paternal Inheritance, Pedigree, Polymorphism, Single Nucleotide, Receptor, Fibroblast Growth Factor, Type 2, Signal Transduction, T-Box Domain Proteins},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2018.12.010},
	author = {Karolak, Justyna A and Vincent, Marie and Deutsch, Gail and Gambin, Tomasz and Cogn{\'e}, Benjamin and Pichon, Olivier and Vetrini, Francesco and Mefford, Heather C and Dines, Jennifer N and Golden-Grant, Katie and Dipple, Katrina and Freed, Amanda S and Leppig, Kathleen A and Dishop, Megan and Mowat, David and Bennetts, Bruce and Gifford, Andrew J and Weber, Martin A and Lee, Anna F and Boerkoel, Cornelius F and Bartell, Tina M and Ward-Melver, Catherine and Besnard, Thomas and Petit, Florence and Bache, Iben and T{\"u}mer, Zeynep and Denis-Musquer, Marie and Joubert, Madeleine and Martinovic, Jelena and B{\'e}n{\'e}teau, Claire and Molin, Arnaud and Carles, Dominique and Andr{\'e}, Gwenaelle and Bieth, Eric and Chassaing, Nicolas and Devisme, Louise and Chalabreysse, Lara and Pasquier, Laurent and Secq, V{\'e}ronique and Don, Massimiliano and Orsaria, Maria and Missirian, Chantal and Mortreux, J{\'e}r{\'e}mie and Sanlaville, Damien and Pons, Linda and K{\"u}ry, S{\'e}bastien and B{\'e}zieau, St{\'e}phane and Liet, Jean-Michel and Joram, Nicolas and Bihou{\'e}e, Tiphaine and Scott, Daryl A and Brown, Chester W and Scaglia, Fernando and Tsai, Anne Chun-Hui and Grange, Dorothy K and Phillips, John A and Pfotenhauer, Jean P and Jhangiani, Shalini N and Gonzaga-Jauregui, Claudia G and Chung, Wendy K and Schauer, Galen M and Lipson, Mark H and Mercer, Catherine L and van Haeringen, Arie and Liu, Qian and Popek, Edwina and Coban Akdemir, Zeynep H and Lupski, James R and Szafranski, Przemyslaw and Isidor, Bertrand and Le Caignec, Cedric and Stankiewicz, Pawe{\l}}
}
@article {67,
	title = {Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.},
	journal = {Hum Genet},
	volume = {135},
	year = {2016},
	month = {2016 May},
	pages = {569-586},
	abstract = {<p>Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV. </p>},
	keywords = {Chromosomes, Human, Pair 16, Comparative Genomic Hybridization, Female, Forkhead Transcription Factors, Genes, Lethal, Genome, Human, Genomic Imprinting, High-Throughput Nucleotide Sequencing, Humans, Infant, Newborn, Male, Pedigree, Persistent Fetal Circulation Syndrome, Pulmonary Alveoli, Pulmonary Veins, Sequence Deletion},
	issn = {1432-1203},
	doi = {10.1007/s00439-016-1655-9},
	author = {Szafranski, Przemyslaw and Gambin, Tomasz and Dharmadhikari, Avinash V and Akdemir, Kadir Caner and Jhangiani, Shalini N and Schuette, Jennifer and Godiwala, Nihal and Yatsenko, Svetlana A and Sebastian, Jessica and Madan-Khetarpal, Suneeta and Surti, Urvashi and Abellar, Rosanna G and Bateman, David A and Wilson, Ashley L and Markham, Melinda H and Slamon, Jill and Santos-Simarro, Fernando and Palomares, Mar{\'\i}a and Nevado, Juli{\'a}n and Lapunzina, Pablo and Chung, Brian Hon-Yin and Wong, Wai-Lap and Chu, Yoyo Wing Yiu and Mok, Gary Tsz Kin and Kerem, Eitan and Reiter, Joel and Ambalavanan, Namasivayam and Anderson, Scott A and Kelly, David R and Shieh, Joseph and Rosenthal, Taryn C and Scheible, Kristin and Steiner, Laurie and Iqbal, M Anwar and McKinnon, Margaret L and Hamilton, Sara Jane and Schlade-Bartusiak, Kamilla and English, Dawn and Hendson, Glenda and Roeder, Elizabeth R and DeNapoli, Thomas S and Littlejohn, Rebecca Okashah and Wolff, Daynna J and Wagner, Carol L and Yeung, Alison and Francis, David and Fiorino, Elizabeth K and Edelman, Morris and Fox, Joyce and Hayes, Denise A and Janssens, Sandra and De Baere, Elfride and Menten, Bj{\"o}rn and Loccufier, Anne and Vanwalleghem, Lieve and Moerman, Philippe and Sznajer, Yves and Lay, Amy S and Kussmann, Jennifer L and Chawla, Jasneek and Payton, Diane J and Phillips, Gael E and Brosens, Erwin and Tibboel, Dick and de Klein, Annelies and Maystadt, Isabelle and Fisher, Richard and Sebire, Neil and Male, Alison and Chopra, Maya and Pinner, Jason and Malcolm, Girvan and Peters, Gregory and Arbuckle, Susan and Lees, Melissa and Mead, Zoe and Quarrell, Oliver and Sayers, Richard and Owens, Martina and Shaw-Smith, Charles and Lioy, Janet and McKay, Eileen and de Leeuw, Nicole and Feenstra, Ilse and Spruijt, Liesbeth and Elmslie, Frances and Thiruchelvam, Timothy and Bacino, Carlos A and Langston, Claire and Lupski, James R and Sen, Partha and Popek, Edwina and Stankiewicz, Pawe{\l}}
}
