Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Harvard

Karolak, JA, Vincent, M, Deutsch, G, Gambin, T, Cogné, B, Pichon, O, Vetrini, F, Mefford, HC, Dines, JN, Golden-Grant, K, Dipple, K, Freed, AS, Leppig, KA, Dishop, M, Mowat, D, Bennetts, B, Gifford, AJ, Weber, MA, Lee, AF, Boerkoel, CF, Bartell, TM, Ward-Melver, C, Besnard, T, Petit, F, Bache, I, Tümer, Z, Denis-Musquer, M, Joubert, M, Martinovic, J, Bénéteau, C, Molin, A, Carles, D, André, G, Bieth, E, Chassaing, N, Devisme, L, Chalabreysse, L, Pasquier, L, Secq, V, Don, M, Orsaria, M, Missirian, C, Mortreux, J, Sanlaville, D, Pons, L, Küry, S, Bézieau, S, Liet, J-M, Joram, N, Bihouée, T, Scott, DA, Brown, CW, Scaglia, F, Tsai, AC-H, Grange, DK, Phillips, JA, Pfotenhauer, JP, Jhangiani, SN, Gonzaga-Jauregui, CG, Chung, WK, Schauer, GM, Lipson, MH, Mercer, CL, van Haeringen, A, Liu, Q, Popek, E, Coban Akdemir, ZH, Lupski, JR, Szafranski, P, Isidor, B, Le Caignec, C & Stankiewicz, P 2019, 'Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway' American Journal of Human Genetics, bind 104, nr. 2, s. 213-228. https://doi.org/10.1016/j.ajhg.2018.12.010

APA

Karolak, J. A., Vincent, M., Deutsch, G., Gambin, T., Cogné, B., Pichon, O., ... Stankiewicz, P. (2019). Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway. American Journal of Human Genetics, 104(2), 213-228. https://doi.org/10.1016/j.ajhg.2018.12.010

CBE

Karolak JA, Vincent M, Deutsch G, Gambin T, Cogné B, Pichon O, Vetrini F, Mefford HC, Dines JN, Golden-Grant K, Dipple K, Freed AS, Leppig KA, Dishop M, Mowat D, Bennetts B, Gifford AJ, Weber MA, Lee AF, Boerkoel CF, Bartell TM, Ward-Melver C, Besnard T, Petit F, Bache I, Tümer Z, Denis-Musquer M, Joubert M, Martinovic J, Bénéteau C, Molin A, Carles D, André G, Bieth E, Chassaing N, Devisme L, Chalabreysse L, Pasquier L, Secq V, Don M, Orsaria M, Missirian C, Mortreux J, Sanlaville D, Pons L, Küry S, Bézieau S, Liet J-M, Joram N, Bihouée T, Scott DA, Brown CW, Scaglia F, Tsai AC-H, Grange DK, Phillips JA, Pfotenhauer JP, Jhangiani SN, Gonzaga-Jauregui CG, Chung WK, Schauer GM, Lipson MH, Mercer CL, van Haeringen A, Liu Q, Popek E, Coban Akdemir ZH, Lupski JR, Szafranski P, Isidor B, Le Caignec C, Stankiewicz P. 2019. Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway. American Journal of Human Genetics. 104(2):213-228. https://doi.org/10.1016/j.ajhg.2018.12.010

MLA

Vancouver

Author

Karolak, Justyna A ; Vincent, Marie ; Deutsch, Gail ; Gambin, Tomasz ; Cogné, Benjamin ; Pichon, Olivier ; Vetrini, Francesco ; Mefford, Heather C ; Dines, Jennifer N ; Golden-Grant, Katie ; Dipple, Katrina ; Freed, Amanda S ; Leppig, Kathleen A ; Dishop, Megan ; Mowat, David ; Bennetts, Bruce ; Gifford, Andrew J ; Weber, Martin A ; Lee, Anna F ; Boerkoel, Cornelius F ; Bartell, Tina M ; Ward-Melver, Catherine ; Besnard, Thomas ; Petit, Florence ; Bache, Iben ; Tümer, Zeynep ; Denis-Musquer, Marie ; Joubert, Madeleine ; Martinovic, Jelena ; Bénéteau, Claire ; Molin, Arnaud ; Carles, Dominique ; André, Gwenaelle ; Bieth, Eric ; Chassaing, Nicolas ; Devisme, Louise ; Chalabreysse, Lara ; Pasquier, Laurent ; Secq, Véronique ; Don, Massimiliano ; Orsaria, Maria ; Missirian, Chantal ; Mortreux, Jérémie ; Sanlaville, Damien ; Pons, Linda ; Küry, Sébastien ; Bézieau, Stéphane ; Liet, Jean-Michel ; Joram, Nicolas ; Bihouée, Tiphaine ; Scott, Daryl A ; Brown, Chester W ; Scaglia, Fernando ; Tsai, Anne Chun-Hui ; Grange, Dorothy K ; Phillips, John A ; Pfotenhauer, Jean P ; Jhangiani, Shalini N ; Gonzaga-Jauregui, Claudia G ; Chung, Wendy K ; Schauer, Galen M ; Lipson, Mark H ; Mercer, Catherine L ; van Haeringen, Arie ; Liu, Qian ; Popek, Edwina ; Coban Akdemir, Zeynep H ; Lupski, James R ; Szafranski, Przemyslaw ; Isidor, Bertrand ; Le Caignec, Cedric ; Stankiewicz, Paweł. / Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway. I: American Journal of Human Genetics. 2019 ; Bind 104, Nr. 2. s. 213-228.

Bibtex

@article{62d96b1de1b34fb0b8772554636ffca9,
title = "Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway",
abstract = "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.",
author = "Karolak, {Justyna A} and Marie Vincent and Gail Deutsch and Tomasz Gambin and Benjamin Cogn{\'e} and Olivier Pichon and Francesco Vetrini and Mefford, {Heather C} and Dines, {Jennifer N} and Katie Golden-Grant and Katrina Dipple and Freed, {Amanda S} and Leppig, {Kathleen A} and Megan Dishop and David Mowat and Bruce Bennetts and Gifford, {Andrew J} and Weber, {Martin A} and Lee, {Anna F} and Boerkoel, {Cornelius F} and Bartell, {Tina M} and Catherine Ward-Melver and Thomas Besnard and Florence Petit and Iben Bache and Zeynep T{\"u}mer and Marie Denis-Musquer and Madeleine Joubert and Jelena Martinovic and Claire B{\'e}n{\'e}teau and Arnaud Molin and Dominique Carles and Gwenaelle Andr{\'e} and Eric Bieth and Nicolas Chassaing and Louise Devisme and Lara Chalabreysse and Laurent Pasquier and V{\'e}ronique Secq and Massimiliano Don and Maria Orsaria and Chantal Missirian and J{\'e}r{\'e}mie Mortreux and Damien Sanlaville and Linda Pons and S{\'e}bastien K{\"u}ry and St{\'e}phane B{\'e}zieau and Jean-Michel Liet and Nicolas Joram and Tiphaine Bihou{\'e}e and Scott, {Daryl A} and Brown, {Chester W} and Fernando Scaglia 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 Qian Liu and Edwina Popek and {Coban Akdemir}, {Zeynep H} and Lupski, {James R} and Przemyslaw Szafranski and Bertrand Isidor and {Le Caignec}, Cedric and Paweł Stankiewicz",
note = "Copyright {\circledC} 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.",
year = "2019",
month = "2",
day = "7",
doi = "10.1016/j.ajhg.2018.12.010",
language = "English",
volume = "104",
pages = "213--228",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway

AU - Karolak, Justyna A

AU - Vincent, Marie

AU - Deutsch, Gail

AU - Gambin, Tomasz

AU - Cogné, Benjamin

AU - Pichon, Olivier

AU - Vetrini, Francesco

AU - Mefford, Heather C

AU - Dines, Jennifer N

AU - Golden-Grant, Katie

AU - Dipple, Katrina

AU - Freed, Amanda S

AU - Leppig, Kathleen A

AU - Dishop, Megan

AU - Mowat, David

AU - Bennetts, Bruce

AU - Gifford, Andrew J

AU - Weber, Martin A

AU - Lee, Anna F

AU - Boerkoel, Cornelius F

AU - Bartell, Tina M

AU - Ward-Melver, Catherine

AU - Besnard, Thomas

AU - Petit, Florence

AU - Bache, Iben

AU - Tümer, Zeynep

AU - Denis-Musquer, Marie

AU - Joubert, Madeleine

AU - Martinovic, Jelena

AU - Bénéteau, Claire

AU - Molin, Arnaud

AU - Carles, Dominique

AU - André, Gwenaelle

AU - Bieth, Eric

AU - Chassaing, Nicolas

AU - Devisme, Louise

AU - Chalabreysse, Lara

AU - Pasquier, Laurent

AU - Secq, Véronique

AU - Don, Massimiliano

AU - Orsaria, Maria

AU - Missirian, Chantal

AU - Mortreux, Jérémie

AU - Sanlaville, Damien

AU - Pons, Linda

AU - Küry, Sébastien

AU - Bézieau, Stéphane

AU - Liet, Jean-Michel

AU - Joram, Nicolas

AU - Bihouée, Tiphaine

AU - Scott, Daryl A

AU - Brown, Chester W

AU - Scaglia, Fernando

AU - Tsai, Anne Chun-Hui

AU - Grange, Dorothy K

AU - Phillips, John A

AU - Pfotenhauer, Jean P

AU - Jhangiani, Shalini N

AU - Gonzaga-Jauregui, Claudia G

AU - Chung, Wendy K

AU - Schauer, Galen M

AU - Lipson, Mark H

AU - Mercer, Catherine L

AU - van Haeringen, Arie

AU - Liu, Qian

AU - Popek, Edwina

AU - Coban Akdemir, Zeynep H

AU - Lupski, James R

AU - Szafranski, Przemyslaw

AU - Isidor, Bertrand

AU - Le Caignec, Cedric

AU - Stankiewicz, Paweł

N1 - Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

PY - 2019/2/7

Y1 - 2019/2/7

N2 - 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.

AB - 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.

U2 - 10.1016/j.ajhg.2018.12.010

DO - 10.1016/j.ajhg.2018.12.010

M3 - Journal article

VL - 104

SP - 213

EP - 228

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 2

ER -

ID: 58250184