@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 {354,
	title = {Loss of carbonic anhydrase XII function in individuals with elevated sweat chloride concentration and pulmonary airway disease.},
	journal = {Hum Mol Genet},
	volume = {25},
	year = {2016},
	month = {2016 05 15},
	pages = {1923-1933},
	abstract = {<p>Elevated sweat chloride levels, failure to thrive (FTT), and lung disease are characteristic features of cystic fibrosis (CF, OMIM $\#$219700). Here we describe variants in CA12 encoding carbonic anhydrase XII in two pedigrees exhibiting CF-like phenotypes. Exome sequencing of a white American adult diagnosed with CF due to elevated sweat chloride, recurrent hyponatremia, infantile FTT and lung disease identified deleterious variants in each CA12 gene: c.908-1 G>A in a splice acceptor and a novel frameshift insertion c.859_860insACCT. In an unrelated consanguineous Omani family, two children with elevated sweat chloride, infantile FTT, and recurrent hyponatremia were homozygous for a novel missense variant (p.His121Gln). Deleterious CFTR variants were absent in both pedigrees. CA XII protein was localized apically in human bronchiolar epithelia and basolaterally in the reabsorptive duct of human sweat glands. Respiratory epithelial cell RNA from the adult proband revealed only aberrant CA12 transcripts and in vitro analysis showed greatly reduced CA XII protein. Studies of ion transport across respiratory epithelial cells in vivo and in culture revealed intact CFTR-mediated chloride transport in the adult proband. CA XII protein bearing either p.His121Gln or a previously identified p.Glu143Lys missense variant localized to the basolateral membranes of polarized Madin-Darby canine kidney (MDCK) cells, but enzyme activity was severely diminished when assayed at physiologic concentrations of extracellular chloride. Our findings indicate that loss of CA XII function should be considered in individuals without CFTR mutations who exhibit CF-like features in the sweat gland and lung.</p>},
	keywords = {Adolescent, Adult, Animals, Carbonic Anhydrases, Child, Child, Preschool, Chlorides, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Dogs, Female, Gene Expression Regulation, Enzymologic, Homozygote, Humans, Lung, Lung Diseases, Madin Darby Canine Kidney Cells, Male, Mutation, Pedigree, Phenotype, Sweat},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddw065},
	author = {Lee, Melissa and Vecchio-Pag{\'a}n, Briana and Sharma, Neeraj and Waheed, Abdul and Li, Xiaopeng and Raraigh, Karen S and Robbins, Sarah and Han, Sangwoo T and Franca, Arianna L and Pellicore, Matthew J and Evans, Taylor A and Arcara, Kristin M and Nguyen, Hien and Luan, Shan and Belchis, Deborah and Hertecant, Jozef and Zabner, Joseph and Sly, William S and Cutting, Garry R}
}
