Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins
- Author
- Przemyslaw Szafranski, Tomasz Gambin, Avinash V Dharmadhikari, Kadir Caner Akdemir, Shalini N Jhangiani, Jennifer Schuette, Nihal Godiwala, Svetlana A Yatsenko, Jessica Sebastian, Suneeta Madan-Khetarpal, Urvashi Surti, Rosanna G Abellar, David A Bateman, Ashley L Wilson, Melinda H Markham, Jill Slamon, Fernando Santos-Simarro, María Palomares, Julián Nevado, Pablo Lapunzina, Brian Hon-Yin Chung, Wai-Lap Wong, Yoyo Wing Yiu Chu, Gary Tsz Kin Mok, Eitan Kerem, Joel Reiter, Namasivayam Ambalavanan, Scott A Anderson, David R Kelly, Joseph Shieh, Taryn C Rosenthal, Kristin Scheible, Laurie Steiner, M Anwar Iqbal, Margaret L McKinnon, Sara Jane Hamilton, Kamilla Schlade-Bartusiak, Dawn English, Glenda Hendson, Elizabeth R Roeder, Thomas S DeNapoli, Rebecca Okashah Littlejohn, Daynna J Wolff, Carol L Wagner, Alison Yeung, David Francis, Elizabeth K Fiorino, Morris Edelman, Joyce Fox, Denise A Hayes, Sandra Janssens (UGent) , Elfride De Baere (UGent) , Björn Menten (UGent) , Anne Loccufier, Lieve Vanwalleghem, Philippe Moerman, Yves Sznajer, Amy S Lay, Jennifer L Kussmann, Jasneek Chawla, Diane J Payton, Gael E Phillips, Erwin Brosens, Dick Tibboel, Annelies de Klein, Isabelle Maystadt, Richard Fisher, Neil Sebire, Alison Male, Maya Chopra, Jason Pinner, Girvan Malcolm, Gregory Peters, Susan Arbuckle, Melissa Lees, Zoe Mead, Oliver Quarrell, Richard Sayers, Martina Owens, Charles Shaw-Smith, Janet Lioy, Eileen Mckay, Nicole de Leeuw, Ilse Feenstra, Liesbeth Spruijt, Frances Elmslie, Timothy Thiruchelvam, Carlos A Bacino, Claire Langston, James R Lupski, Partha Sen, Edwina Popek and Pawel Stankiewicz
- Organization
- Abstract
- 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.
- Keywords
- CONGENITAL HEART-DISEASE, ENHANCER FACTOR-2 MEF2, LUNG DEVELOPMENTAL DISORDER, FOXF1, GENE, EXPRESSION, COPY-NUMBER VARIANTS, RING FINGER PROTEIN, UNIPARENTAL DISOMY, SOMATIC MOSAICISM
Downloads
-
(...).pdf
- full text
- |
- UGent only
- |
- |
- 5.33 MB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8099610
- MLA
- Szafranski, Przemyslaw, et al. “Pathogenetics of Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins.” HUMAN GENETICS, vol. 135, no. 5, 2016, pp. 569–86, doi:10.1007/s00439-016-1655-9.
- APA
- Szafranski, P., Gambin, T., Dharmadhikari, A. V., Akdemir, K. C., Jhangiani, S. N., Schuette, J., … Stankiewicz, P. (2016). Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins. HUMAN GENETICS, 135(5), 569–586. https://doi.org/10.1007/s00439-016-1655-9
- Chicago author-date
- Szafranski, Przemyslaw, Tomasz Gambin, Avinash V Dharmadhikari, Kadir Caner Akdemir, Shalini N Jhangiani, Jennifer Schuette, Nihal Godiwala, et al. 2016. “Pathogenetics of Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins.” HUMAN GENETICS 135 (5): 569–86. https://doi.org/10.1007/s00439-016-1655-9.
- Chicago author-date (all authors)
- Szafranski, Przemyslaw, Tomasz Gambin, Avinash V Dharmadhikari, Kadir Caner Akdemir, Shalini N Jhangiani, Jennifer Schuette, Nihal Godiwala, Svetlana A Yatsenko, Jessica Sebastian, Suneeta Madan-Khetarpal, Urvashi Surti, Rosanna G Abellar, David A Bateman, Ashley L Wilson, Melinda H Markham, Jill Slamon, Fernando Santos-Simarro, María Palomares, Julián Nevado, Pablo Lapunzina, Brian Hon-Yin Chung, Wai-Lap Wong, Yoyo Wing Yiu Chu, Gary Tsz Kin Mok, Eitan Kerem, Joel Reiter, Namasivayam Ambalavanan, Scott A Anderson, David R Kelly, Joseph Shieh, Taryn C Rosenthal, Kristin Scheible, Laurie Steiner, M Anwar Iqbal, Margaret L McKinnon, Sara Jane Hamilton, Kamilla Schlade-Bartusiak, Dawn English, Glenda Hendson, Elizabeth R Roeder, Thomas S DeNapoli, Rebecca Okashah Littlejohn, Daynna J Wolff, Carol L Wagner, Alison Yeung, David Francis, Elizabeth K Fiorino, Morris Edelman, Joyce Fox, Denise A Hayes, Sandra Janssens, Elfride De Baere, Björn Menten, Anne Loccufier, Lieve Vanwalleghem, Philippe Moerman, Yves Sznajer, Amy S Lay, Jennifer L Kussmann, Jasneek Chawla, Diane J Payton, Gael E Phillips, Erwin Brosens, Dick Tibboel, Annelies de Klein, Isabelle Maystadt, Richard Fisher, Neil Sebire, Alison Male, Maya Chopra, Jason Pinner, Girvan Malcolm, Gregory Peters, Susan Arbuckle, Melissa Lees, Zoe Mead, Oliver Quarrell, Richard Sayers, Martina Owens, Charles Shaw-Smith, Janet Lioy, Eileen Mckay, Nicole de Leeuw, Ilse Feenstra, Liesbeth Spruijt, Frances Elmslie, Timothy Thiruchelvam, Carlos A Bacino, Claire Langston, James R Lupski, Partha Sen, Edwina Popek, and Pawel Stankiewicz. 2016. “Pathogenetics of Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins.” HUMAN GENETICS 135 (5): 569–586. doi:10.1007/s00439-016-1655-9.
- Vancouver
- 1.Szafranski P, Gambin T, Dharmadhikari AV, Akdemir KC, Jhangiani SN, Schuette J, et al. Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins. HUMAN GENETICS. 2016;135(5):569–86.
- IEEE
- [1]P. Szafranski et al., “Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins,” HUMAN GENETICS, vol. 135, no. 5, pp. 569–586, 2016.
@article{8099610, abstract = {{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.}}, 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, María and Nevado, Julián 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, Björn 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, Pawel}}, issn = {{0340-6717}}, journal = {{HUMAN GENETICS}}, keywords = {{CONGENITAL HEART-DISEASE,ENHANCER FACTOR-2 MEF2,LUNG DEVELOPMENTAL DISORDER,FOXF1,GENE,EXPRESSION,COPY-NUMBER VARIANTS,RING FINGER PROTEIN,UNIPARENTAL DISOMY,SOMATIC MOSAICISM}}, language = {{eng}}, number = {{5}}, pages = {{569--586}}, title = {{Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins}}, url = {{http://doi.org/10.1007/s00439-016-1655-9}}, volume = {{135}}, year = {{2016}}, }
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: