Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

2.50
Hdl Handle:
http://hdl.handle.net/11287/605270
Title:
Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.
Authors:
Szafranski, P.; Gambin, T.; Dharmadhikari, A. V.; Akdemir, K. C.; Jhangiani, S. N.; Schuette, J.; Godiwala, N.; Yatsenko, S. A.; Sebastian, J.; Madan-Khetarpal, S.; Surti, U.; Abellar, R. G.; Bateman, D. A.; Wilson, A. L.; Markham, M. H.; Slamon, J.; Santos-Simarro, F.; Palomares, M.; Nevado, J.; Lapunzina, P.; Chung, B. Hon-Yin; Wong, W-L; Chu, Y.W. Y.; Mok, G. T. K.; Kerem, E.; Reiter, J.; Ambalavanan, N.; Anderson, S. A.; Kelly, D. R.; Shieh, J.; Rosenthal, T. C.; Scheible, K.; Steiner, L.; Iqbal, M. A.; McKinnon, M. L.; Hamilton, S. J.; Schlade-Bartusiak, K.; English, D.; Hendson, G.; Roeder, E. R.; DeNapoli, T. S.; Littlejohn, R. O.; Wolff, D. J.; Wagner, C. L.; Yeung, A.; Francis, D.; Fiorino, E. K.; Edelman, M.; Fox, J.; Hayes, D. A.; Janssens, S.; De Baere, E.; Menten, B.; Loccufier, A.; Vanwalleghem, L.; Moerman, P.; Sznajer, Y.; Lay, A. S.; Kussmann, J. L.; Chawla, J.; Payton, D. J.; Phillips, G. E.; Brosens, E.; Tibboel, D.; de Klein, A.; Maystadt, I.; Fisher, R.; Sebire, N.; Male, A.; Chopra, M.; Pinner, J.; Malcolm, G.; Peters, G.; Arbuckle, S.; Lees, M.; Mead, Z.; Quarrell, O.; Sayers, R.; Owens, Martina; Shaw-Smith, Charles; Lioy, J.; McKay, E.; de Leeuw, N.; Feenstra, I.; Spruijt, L.; Elmslie, F.; Thiruchelvam, T.; Bacino, C. A.; Langston, C.; Lupski, J. R.; Sen, P.; Popek, E.; Stankiewicz, P.
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.
Citation:
Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins. 2016 May;135(5):569-86
Publisher:
Springer
Journal:
Human genetics
Issue Date:
12-Apr-2016
URI:
http://hdl.handle.net/11287/605270
DOI:
10.1007/s00439-016-1655-9
PubMed ID:
27071622
Additional Links:
http://link.springer.com/article/10.1007/s00439-016-1655-9
Type:
Journal Article
Language:
en
ISSN:
1432-1203
Appears in Collections:
Molecular Genetics; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorSzafranski, P.en
dc.contributor.authorGambin, T.en
dc.contributor.authorDharmadhikari, A. V.en
dc.contributor.authorAkdemir, K. C.en
dc.contributor.authorJhangiani, S. N.en
dc.contributor.authorSchuette, J.en
dc.contributor.authorGodiwala, N.en
dc.contributor.authorYatsenko, S. A.en
dc.contributor.authorSebastian, J.en
dc.contributor.authorMadan-Khetarpal, S.en
dc.contributor.authorSurti, U.en
dc.contributor.authorAbellar, R. G.en
dc.contributor.authorBateman, D. A.en
dc.contributor.authorWilson, A. L.en
dc.contributor.authorMarkham, M. H.en
dc.contributor.authorSlamon, J.en
dc.contributor.authorSantos-Simarro, F.en
dc.contributor.authorPalomares, M.en
dc.contributor.authorNevado, J.en
dc.contributor.authorLapunzina, P.en
dc.contributor.authorChung, B. Hon-Yinen
dc.contributor.authorWong, W-Len
dc.contributor.authorChu, Y.W. Y.en
dc.contributor.authorMok, G. T. K.en
dc.contributor.authorKerem, E.en
dc.contributor.authorReiter, J.en
dc.contributor.authorAmbalavanan, N.en
dc.contributor.authorAnderson, S. A.en
dc.contributor.authorKelly, D. R.en
dc.contributor.authorShieh, J.en
dc.contributor.authorRosenthal, T. C.en
dc.contributor.authorScheible, K.en
dc.contributor.authorSteiner, L.en
dc.contributor.authorIqbal, M. A.en
dc.contributor.authorMcKinnon, M. L.en
dc.contributor.authorHamilton, S. J.en
dc.contributor.authorSchlade-Bartusiak, K.en
dc.contributor.authorEnglish, D.en
dc.contributor.authorHendson, G.en
dc.contributor.authorRoeder, E. R.en
dc.contributor.authorDeNapoli, T. S.en
dc.contributor.authorLittlejohn, R. O.en
dc.contributor.authorWolff, D. J.en
dc.contributor.authorWagner, C. L.en
dc.contributor.authorYeung, A.en
dc.contributor.authorFrancis, D.en
dc.contributor.authorFiorino, E. K.en
dc.contributor.authorEdelman, M.en
dc.contributor.authorFox, J.en
dc.contributor.authorHayes, D. A.en
dc.contributor.authorJanssens, S.en
dc.contributor.authorDe Baere, E.en
dc.contributor.authorMenten, B.en
dc.contributor.authorLoccufier, A.en
dc.contributor.authorVanwalleghem, L.en
dc.contributor.authorMoerman, P.en
dc.contributor.authorSznajer, Y.en
dc.contributor.authorLay, A. S.en
dc.contributor.authorKussmann, J. L.en
dc.contributor.authorChawla, J.en
dc.contributor.authorPayton, D. J.en
dc.contributor.authorPhillips, G. E.en
dc.contributor.authorBrosens, E.en
dc.contributor.authorTibboel, D.en
dc.contributor.authorde Klein, A.en
dc.contributor.authorMaystadt, I.en
dc.contributor.authorFisher, R.en
dc.contributor.authorSebire, N.en
dc.contributor.authorMale, A.en
dc.contributor.authorChopra, M.en
dc.contributor.authorPinner, J.en
dc.contributor.authorMalcolm, G.en
dc.contributor.authorPeters, G.en
dc.contributor.authorArbuckle, S.en
dc.contributor.authorLees, M.en
dc.contributor.authorMead, Z.en
dc.contributor.authorQuarrell, O.en
dc.contributor.authorSayers, R.en
dc.contributor.authorOwens, Martinaen
dc.contributor.authorShaw-Smith, Charlesen
dc.contributor.authorLioy, J.en
dc.contributor.authorMcKay, E.en
dc.contributor.authorde Leeuw, N.en
dc.contributor.authorFeenstra, I.en
dc.contributor.authorSpruijt, L.en
dc.contributor.authorElmslie, F.en
dc.contributor.authorThiruchelvam, T.en
dc.contributor.authorBacino, C. A.en
dc.contributor.authorLangston, C.en
dc.contributor.authorLupski, J. R.en
dc.contributor.authorSen, P.en
dc.contributor.authorPopek, E.en
dc.contributor.authorStankiewicz, P.en
dc.date.accessioned2016-04-14T15:44:18Zen
dc.date.available2016-04-14T15:44:18Zen
dc.date.issued2016-04-12en
dc.identifier.citationPathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins. 2016 May;135(5):569-86en
dc.identifier.issn1432-1203en
dc.identifier.pmid27071622en
dc.identifier.doi10.1007/s00439-016-1655-9en
dc.identifier.urihttp://hdl.handle.net/11287/605270en
dc.description.abstractAlveolar 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.en
dc.languageENGen
dc.language.isoenen
dc.publisherSpringeren
dc.relation.urlhttp://link.springer.com/article/10.1007/s00439-016-1655-9en
dc.rightsArchived with thanks to Human geneticsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titlePathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.en
dc.typeJournal Articleen
dc.identifier.journalHuman geneticsen
dc.type.versionIn press (epub ahead of print)en

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