Identifying new potential genetic biomarkers for HELLP syndrome using massive parallel sequencing

dc.contributorLaissue, Paul
dc.contributorArdila-Montealegre, Javier
dc.contributorSerrano, Norma
dc.contributorGENIUROS
dc.creatorGómez-Murcia, Tatiana
dc.creatorAguirre-García, Angel
dc.date.accessioned2021-08-19T15:28:37Z
dc.date.accessioned2022-09-22T14:42:06Z
dc.date.available2021-08-19T15:28:37Z
dc.date.available2022-09-22T14:42:06Z
dc.date.created2021-08-19T15:28:37Z
dc.identifierhttps://repository.urosario.edu.co/handle/10336/32279
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/3441379
dc.description.abstractBackground: Preeclampsia (PE) is a frequently occurring multisystemic disease affecting ~5% of pregnancies. PE patients may develop HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet), a mother and foetus life-threatening condition. Research into HELLP’s genetic origin has been relatively unsuccessful, mainly because normal placental function and blood pressure regulation involve the fine-regulation of hundreds of genes. Objective: To identify new genes and mutations constituting potential biomarkers for HELLP syndrome. Study design: The present case-control study involved whole-exome sequencing of 79 unrelated HELLP women. Candidate variants were screened in a control population constituted by 176 individuals. Stringent bioinformatics filters were used for selecting potentially etiological sequence variants in a subset of 487 genes. We used robust in silico mutation modelling for predicting the potential effect on protein structure. Results: We identified numerous sequence variants in genes related to angiogenesis/coagulation/blood pressure regulation, cell differentiation/communication/adhesion, cell cycle and transcriptional gene regulation, extracellular matrix biology, lipid metabolism and immunological response. Five sequence variants generated premature stop codons in genes playing an essential role in placental physiology (STOX1, PDGFD, IGF2, MMP1 and DNAH11). Six variants (ERAP1- p.Ile915Thr, ERAP2- p.Leu837Ser, COMT-p.His192Gln, CSAD-p.Pro418Ser, CDH1- p.Ala298Thr and CCR2-p.Met249Lys) led to destabilisation of protein structure as they had significant energy and residue interaction-related changes. We identified at least two mutations in 57% of patients, arguing in favour of a polygenic origin for the HELLP syndrome. Conclusion: Our results provide novel evidence regarding PE/HELLP’s genetic origin, leading to new biomarkers, having potential clinical usefulness, being proposed.
dc.languageeng
dc.publisherUniversidad del Rosario
dc.publisherEspecialización en Ginecología y Obstericia
dc.publisherEscuela de Medicina y Ciencias de la Salud
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.rightsBloqueado (Texto referencial)
dc.rightsEL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma. PARGRAFO: En caso de presentarse cualquier reclamación o acción por parte de un tercero en cuanto a los derechos de autor sobre la obra en cuestión, EL AUTOR, asumirá toda la responsabilidad, y saldrá en defensa de los derechos aquí autorizados; para todos los efectos la universidad actúa como un tercero de buena fe. EL AUTOR, autoriza a LA UNIVERSIDAD DEL ROSARIO, para que en los términos establecidos en la Ley 23 de 1982, Ley 44 de 1993, Decisión andina 351 de 1993, Decreto 460 de 1995 y demás normas generales sobre la materia, utilice y use la obra objeto de la presente autorización. -------------------------------------- POLITICA DE TRATAMIENTO DE DATOS PERSONALES. Declaro que autorizo previa y de forma informada el tratamiento de mis datos personales por parte de LA UNIVERSIDAD DEL ROSARIO para fines académicos y en aplicación de convenios con terceros o servicios conexos con actividades propias de la academia, con estricto cumplimiento de los principios de ley. Para el correcto ejercicio de mi derecho de habeas data cuento con la cuenta de correo habeasdata@urosario.edu.co, donde previa identificación podré solicitar la consulta, corrección y supresión de mis datos.
dc.sourceJ.M. Roberts, G. Pearson, J. Cutler, M. Lindheimer, Summary of the NHLBI working group on research on hypertension during pregnancy, Hypertension 41 (3) (2003) 437–445.
dc.sourceS. Lisonkova, K.S. Joseph, Incidence of preeclampsia: risk factors and outcomes associated with early-versus late-onset disease, Am. J. Obstet. Gynecol. 209 (2013) 544.e1–544.e12.
dc.sourceA. Fraser, S.M. Nelson, C. Macdonald-Wallis, L. Cherry, E. Butler, N. Sattar, D.A. Lawlor, Associations of pregnancy complications with calculated cardiovascular disease risk and cardiovascular risk factors in middle age: the avon longitudinal study of parents and children, Circulation 125 (2012) 1367–1380.
dc.sourceS. Kwiatkowski, B. Dołegowska, E. Kwiatkowska, R. Rzepka, N. Marczuk, B. Loj, A. Torbè, Maternal endothelial damage as a disorder shared by early preeclampsia, late preeclampsia and intrauterine growth restriction, J. Perinat. Med. 45 (2017) 793–802.
dc.sourceT. Chaiworapongsa, P. Chaemsaithong, L. Yeo, R. Romero, Pre-eclampsia part 1: current understanding of its pathophysiology, Nat. Rev. Nephrol. 10 (8) (2014) 466–480.
dc.sourceJ. Jebbink, A. Wolters, F. Fernando, G. Afink, J. van der Post, C. Ris-Stalpers, Molecular genetics of preeclampsia and HELLP syndrome — a review, Biochimica et Biophysica Acta (BBA) – Mol. Basis Dis. 1822 (12) (2012) 1960–1969.
dc.sourceS.T. Chelbi, R.A. Veitia, D. Vaiman, Why preeclampsia still exists? Medical Hypotheses 81 (2) (2013) 259–263.
dc.sourceM. van Dijk, J. van Bezu, D. van Abel, C. Dunk, M.A. Blankenstein, C.B.M. Oudejans, S.J. Lye, The STOX1 genotype associated with pre-eclampsia leads to a reduction of trophoblast invasion by alpha-T-catenin upregulation, Hum. Mol. Genet. 19 (2010) 2658–2667.
dc.sourceE.M. George, G.L. Bidwell, STOX1: a new player in preeclampsia? Hypertension 61 (2013) 561–563.
dc.sourceD. Vaiman, F. Miralles, Targeting STOX1 in the therapy of preeclampsia, Expert Opin. Therapeut. Targets 20 (12) (2016) 1433–1443.
dc.sourceA. Ducat, L. Doridot, R. Calicchio, C. Méhats, J.-L. Vilotte, J. Castille, S. Barbaux, B. Couderc, S. Jacques, F. Letourneur, C. Buffat, F. Le Grand, P. Laissue, F. Miralles, D. Vaiman, Endothelial cell dysfunction and cardiac hypertrophy in the STOX1 model of preeclampsia, Sci. Rep. 6 (2016) 19196.
dc.sourceH. Collinot, C. Marchiol, I. Lagoutte, F. Lager, N. Siauve, G. Autret, D. Balvay, G. Renault, L.J. Salomon, D. Vaiman, Preeclampsia induced by STOX1 overexpression in mice induces intrauterine growth restriction, abnormal ultrasonography and BOLD MRI signatures, J. Hypertens. 36 (6) (2018) 1399–1406.
dc.sourceP. Laissue, B. Lakhal, M. Vatin, F. Batista, G. Burgio, E. Mercier, E.D. Santos, C. Buffat, D.C. Sierra-Diaz, G. Renault, X. Montagutelli, J. Salmon, P. Monget, R.A. Veitia, C. Méhats, M. Fellous, J.-C. Gris, J. Cocquet, D. Vaiman, Association of FOXD1 variants with adverse pregnancy outcomes in mice and humans, Open Biol. 6 (10) (2016) 160109, https://doi.org/10.1098/rsob.160109
dc.sourceP. Quintero-Ronderos, K.M. Jiménez, C. Esteban-Pérez, D.A. Ojeda, S. Bello, D.J. Fonseca, M.A. Coronel, H. Moreno-Ortiz, D.C. Sierra-Díaz, E. Lucena, S. Barbaux, D. Vaiman, P. Laissue, FOXD1 mutations are related to repeated implantation failure, intra-uterine growth restriction and preeclampsia, Mol. Med. 25 (2019) 37.
dc.sourceM. Johnson, M. Løset, S. Brennecke, J. Peralta, T. Dyer, C. East, C. Pennell, R.- C. Huang, T. Mori, L. Beilin, J. Blangero, E. Moses, OS049. Exome sequencing identifies likely functional variantsinfluencing preeclampsia and CVD risk, Pregnancy Hypertens. Int. J. Women's Cardiovasc. Health 2 (3) (2012) 203–204.
dc.sourceT. Kaartokallio, J. Wang, S. Heinonen, E. Kajantie, K. Kivinen, A. Pouta, P. Gerdhem, H. Jiao, J. Kere, H. Laivuori, Exome sequencing in pooled DNA samples to identify maternal pre-eclampsia risk variants, Sci. Rep. 6 (2016) 29085.
dc.sourceA.T. Hansen, J.M.B. Jensen, A.-M. Hvas, M. Christiansen, The genetic component of preeclampsia: a whole-exome sequencing study, PLOS ONE 13 (2018) e0197217.
dc.sourceP.E. Melton, M.P. Johnson, D. Gokhale-Agashe, A.J. Rea, A. Ariff, G. Cadby, J.M. Peralta, T.J. McNab, R.JN. Allcock, L.J. Abraham, J. Blangero, S.P. Brennecke, E.K. Moses, Whole-exome sequencing in multiplex preeclampsia families identifies novel candidate susceptibility genes, J. Hypertens. 37 (5) (2019) 997–1011.
dc.sourceK. Haram, E. Svendsen, U. Abildgaard, The HELLP syndrome: clinical issues and management. A Review, BMC Pregnancy Childbirth 9 (1) (2009), https://doi.org/ 10.1186/1471-2393-9-8.
dc.sourceC. Zhang, S. Liu, Y. Zhou, Accurate and efficient loop selections by the DFIRE-based all-atom statistical potential, Protein Sci. 13 (2004) 391–399.
dc.sourceB. Li, D.J. Liu, S.M. Leal, Identifying rare variants associated with complex traits via sequencing, Curr. Protocols Hum. Genet. 78 (1) (2013), https://doi.org/10.1002/ 0471142905.2013.78.issue-110.1002/0471142905.hg0126s78.
dc.sourceM.J. Emond, T. Louie, J. Emerson, W. Zhao, R.A. Mathias, M.R. Knowles, F.A. Wright, M.J. Rieder, H.K. Tabor, D.A. Nickerson, K.C. Barnes, R.L. Gibson, M.J. Bamshad, Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis, Nat. Genet. 44 (8) (2012) 886–889.
dc.sourceM.J. Emond, T. Louie, J. Emerson, J.X. Chong, R.A. Mathias, M.R. Knowles, M.J. Rieder, H.K. Tabor, D.A. Nickerson, K.C. Barnes, N.G.E.S. Project, L. Go, R.L. Gibson, M.J. Bamshad, Exome sequencing of phenotypic extremes identifies CAV2 and TMC6 as interacting modifiers of chronic pseudomonas aeruginosa infection in cystic fibrosis, PLOS Genet. 11 (2015) e1005273.
dc.sourceA.S. Johar, J.-M. Anaya, D. Andrews, H.R. Patel, M. Field, C. Goodnow, M. Arcos- Burgos, Candidate gene discovery in autoimmunity by using extreme phenotypes, next generation sequencing and whole exome capture, Autoimmun. Rev. 14 (3) (2015) 204–209.
dc.sourceT.A. Manolio, F.S. Collins, N.J. Cox, D.B. Goldstein, L.A. Hindorff, D.J. Hunter, M.I. McCarthy, E.M. Ramos, L.R. Cardon, A. Chakravarti, J.H. Cho, A.E. Guttmacher, A. Kong, L. Kruglyak, E. Mardis, C.N. Rotimi, M. Slatkin, D. Valle, A.S. Whittemore, M. Boehnke, A.G. Clark, E.E. Eichler, G. Gibson, J.L. Haines, T.F.C. Mackay, S.A. McCarroll, P.M. Visscher, Finding the missing heritability of complex diseases, Nature 461 (7265) (2009) 747–753.
dc.sourceS. Lee, Gonçalo R. Abecasis, M. Boehnke, X. Lin, Rare-variant association analysis: study designs and statistical tests, Am. J. Hum. Genet. 95 (1) (2014) 5–23.
dc.sourceL. Bomba, K. Walter, N. Soranzo, The impact of rare and low-frequency genetic variants in common disease, Genome Biol. 18 (2017) 77.
dc.sourceL.C. Patiño, I. Beau, C. Carlosama, J.C. Buitrago, R. González, C.F. Suárez, M.A. Patarroyo, B. Delemer, J. Young, N. Binart, P. Laissue, New mutations in nonsyndromic primary ovarian insufficiency patients identified via whole-exome sequencing, Hum. Reprod. 32 (2017) 1512–1520.
dc.sourceP. Quintero-Ronderos, E. Mercier, M. Fukuda, R. González, C.F. Suárez, M.A. Patarroyo, D. Vaiman, J.-C. Gris, P. Laissue, Novel genes and mutations in patients affected by recurrent pregnancy loss, PLoS ONE. 12 (2017) e0186149.
dc.sourceP. Laissue, The molecular complexity of primary ovarian insufficiency aetiology and the use of massively parallel sequencing, Mol. Cell. Endocrinol. 460 (2018) 170–180.
dc.sourceE.J. Tucker, S. Jaillard, S.R. Grover, J. van den Bergen, G. Robevska, K.M. Bell, S. Sadedin, C. Hanna, J. Dulon, P. Touraine, A.H. Sinclair, TP63-truncating variants cause isolated premature ovarian insufficiency, Hum. Mutat. 40 (2019) 886–892.
dc.sourceC. Delcour, L. Amazit, L.C. Patino, F. Magnin, J. Fagart, B. Delemer, J. Young, P. Laissue, N. Binart, I. Beau, ATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failure, Genet. Med. 21 (4) (2019) 930–938.
dc.sourceL.C. Patiño, I. Beau, A. Morel, B. Delemer, J. Young, N. Binart, P. Laissue, Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency etiology, Hum. Mutation 40 (1) (2019) 25–30.
dc.sourceH. Miyashita, T. Yamazaki, T. Akada, O. Niizeki, M. Ogawa, S. Nishikawa, Y. Sato, A mouse orthologue of puromycin-insensitive leucyl-specific aminopeptidase is expressed in endothelial cells and plays an important role in angiogenesis, Blood. 99 (2002) 3241–3249.
dc.sourceY. Goto, A. Hattori, Y. Ishii, M. Tsujimoto, Reduced activity of the hypertensionassociated Lys528Arg mutant of human adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase-1, FEBS Lett. 580 (2006) 1833–1838.
dc.sourceL. Cifaldi, P. Romania, S. Lorenzi, F. Locatelli, D. Fruci, Role of endoplasmic reticulum aminopeptidases in health and disease: from infection to cancer, Int. J. Mol. Sci. 13 (2012) 8338–8352.
dc.sourceC. Hisatsune, E. Ebisui, M. Usui, N. Ogawa, A. Suzuki, N. Mataga, H. Takahashi- Iwanaga, K. Mikoshiba, ERp44 exerts redox-dependent control of blood pressure at the ER, Mol. Cell 58 (6) (2015) 1015–1027.
dc.sourceY. Goto, K. Ogawa, T.J. Nakamura, A. Hattori, M. Tsujimoto, Substrate-dependent nitric oxide synthesis by secreted endoplasmic reticulum aminopeptidase 1 in macrophages, J. Biochem. 157 (6) (2015) 439–449.
dc.sourceN. Yamamoto, J. Nakayama, K. Yamakawa-Kobayashi, H. Hamaguchi, R. Miyazaki, T. Arinami, Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension, Hum. Mutat. 19 (3) (2002) 251–257.
dc.sourceM.P. Johnson, L.T. Roten, T.D. Dyer, C.E. East, S. Forsmo, J. Blangero, S.P. Brennecke, R. Austgulen, E.K. Moses, The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations, Hum. Genet. 126 (5) (2009) 655–666.
dc.sourceS.A. Founds, Y.P. Conley, J.F. Lyons-Weiler, A. Jeyabalan, W. Allen Hogge, K.P. Conrad, Altered global gene expression in first trimester placentas of women destined to develop preeclampsia, Placenta 30 (1) (2009) 15–24.
dc.sourceL.D. Hill, D.D. Hilliard, T.P. York, S. Srinivas, J.P. Kusanovic, R. Gomez, M.A. Elovitz, R. Romero, J.F. Strauss, Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study, BMC Med. Genet. 12 (2011) 64.
dc.sourceD.L. Vanhille, L.D. Hill, D.D. Hilliard, E.D. Lee, M.E. Teves, S. Srinivas, J.P. Kusanovic, R. Gomez, E. Stratikos, M.A. Elovitz, R. Romero, J.F. Strauss, A novel ERAP2 haplotype structure in a chilean population: implications for ERAP2 protein expression and preeclampsia risk, Mol. Genet. Genom. Med. 1 (2013) 98–107.
dc.sourceT.T. Nguyen, S.-C. Chang, I. Evnouchidou, I.A. York, C. Zikos, K.L. Rock, A.L. Goldberg, E. Stratikos, L.J. Stern, Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1, Nat. Struct. Mol. Biol. 18 (5) (2011) 604–613.
dc.sourceA. Gandhi, D. Lakshminarasimhan, Y. Sun, H.-C. Guo, Structural insights into the molecular ruler mechanism of the endoplasmic reticulum aminopeptidase ERAP1, Sci. Rep. 1 (2011) 186.
dc.sourceG. Kochan, T. Krojer, D. Harvey, R. Fischer, L. Chen, M. Vollmar, F. von Delft, K.L. Kavanagh, M.A. Brown, P. Bowness, P. Wordsworth, B.M. Kessler, U. Oppermann, Crystal structures of the endoplasmic reticulum aminopeptidase-1 (ERAP1) reveal the molecular basis for N-terminal peptide trimming, Proc. Natl. Acad. Sci. 108 (19) (2011) 7745–7750.
dc.sourceL. Sui, A. Gandhi, H.-C. Guo, Crystal structure of a polypeptide’s C-terminus in complex with the regulatory domain of ER aminopeptidase 1, Mol. Immunol. 80 (2016) 41–49.
dc.sourceJ.R. Birtley, E. Saridakis, E. Stratikos, I.M. Mavridis, The crystal structure of human endoplasmic reticulum aminopeptidase 2 reveals the atomic basis for distinct roles in antigen processing, Biochemistry 51 (1) (2012) 286–295.
dc.sourceK. Kanasaki, K. Palmsten, H. Sugimoto, S. Ahmad, Y. Hamano, L. Xie, S. Parry, H.G. Augustin, V.H. Gattone, J. Folkman, J.F. Strauss, R. Kalluri, Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with preeclampsia, Nature 453 (7198) (2008) 1117–1121.
dc.sourceS. Banerjee, H. Randeva, A.E. Chambers, Mouse models for preeclampsia: disruption of redox-regulated signaling, Reprod. Biol. Endocrinol. 7 (1) (2009), https://doi. org/10.1186/1477-7827-7-4.
dc.sourceA. Taravati, F. Tohidi, M. Moniri, K. Kamali, Catechol-O-methyltransferase gene polymorphism (Val158Met) and development of pre-eclampsia, Arch. Med. Res. 48 (2) (2017) 180–186.
dc.sourceA. Ehler, J. Benz, D. Schlatter, M.G. Rudolph, Mapping the conformational space accessible to catechol-O-methyltransferase, Acta Crystallogr. D Biol. Crystallogr. 70 (2014) 2163–2174.
dc.sourceN. Ueki, K. Kanasaki, M. Kanasaki, S. Takeda, D. Koya, Catechol-O-methyltransferase deficiency leads to hypersensitivity of the pressor response against angiotensin II, Hypertension 69 (6) (2017) 1156–1164.
dc.sourceD. Vaiman, R. Calicchio, F. Miralles, Landscape of transcriptional deregulations in the preeclamptic placenta, PLoS ONE 8 (2013) e65498.
dc.sourceM. van Dijk, J. Mulders, A. Poutsma, A.A.M. Könst, A.M.A. Lachmeijer, G.A. Dekker, M.A. Blankenstein, C.B.M. Oudejans, Maternal segregation of the Dutch preeclampsia locus at 10q22 with a new member of the winged helix gene family, Nat. Genet. 37 (5) (2005) 514–519.
dc.sourceV. Rigourd, C. Chauvet, S.T. Chelbi, R. Rebourcet, F. Mondon, F. Letourneur, T.-M. Mignot, S. Barbaux, D. Vaiman, STOX1 overexpression in choriocarcinoma cells mimics transcriptional alterations observed in preeclamptic placentas, PLoS One 3 (2008).
dc.sourceA. Ducat, B. Couderc, A. Bouter, L. Biquard, R. Aouache, B. Passet, L. Doridot, M.- B. Cohen, P. Ribaux, C. Apicella, I. Gaillard, S. Palfray, Y. Chen, A. Vargas, A. Julé, L. Frelin, J. Cocquet, C.R. San Martin, S. Jacques, F. Busato, J. Tost, C. Méhats, P. Laissue, J.-L. Vilotte, F. Miralles, D. Vaiman, Molecular mechanisms of trophoblast dysfunction mediated by imbalance between STOX1 isoforms, iScience 23 (5) (2020) 101086, https://doi.org/10.1016/j.isci.2020.101086.
dc.sourceM. Uutela, M. Wirzenius, K. Paavonen, I. Rajantie, Y. He, T. Karpanen, M. Lohela, H. Wiig, P. Salven, K. Pajusola, U. Eriksson, K. Alitalo, PDGF-D induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis, Blood 104 (2004) 3198–3204.
dc.sourceS. De Falco, The discovery of placenta growth factor and its biological activity, Exp. Mol. Med. 44 (1) (2012) 1, https://doi.org/10.3858/emm.2012.44.1.025.
dc.sourceL. Muhl, E.B. Folestad, H. Gladh, Y. Wang, C. Moessinger, L. Jakobsson, U. Eriksson, Neuropilin 1 binds PDGF-D and is a co-receptor in PDGF-D–PDGFRβ signaling, J. Cell. Sci. 130 (8) (2017) 1365–1378.
dc.sourceF.C. Cassidy, M. Charalambous, Genomic imprinting, growth and maternal–fetal interactions, J. Exp. Biol. 221 (Suppl 1) (2018) jeb164517, https://doi.org/10. 1242/jeb.164517.
dc.sourceM. Begemann, B. Zirn, G. Santen, E. Wirthgen, L. Soellner, H.-M. Büttel, R. Schweizer, W. van Workum, G. Binder, T. Eggermann, Paternally inherited IGF2 mutation and growth restriction, N. Engl. J. Med. 373 (4) (2015) 349–356.
dc.sourceE.L. Wakeling, F. Brioude, O. Lokulo-Sodipe, S.M. O'Connell, J. Salem, J. Bliek, A.P.M. Canton, K.H. Chrzanowska, J.H. Davies, R.P. Dias, B. Dubern, M. Elbracht, E. Giabicani, A. Grimberg, K. Grønskov, A.C.S. Hokken-Koelega, A.A. Jorge, M. Kagami, A. Linglart, M. Maghnie, K. Mohnike, D. Monk, G.E. Moore, P.G. Murray, T. Ogata, I.O. Petit, S. Russo, E. Said, M. Toumba, Z. Tümer, G. Binder, T. Eggermann, M.D. Harbison, I.K. Temple, D.J.G. Mackay, I. Netchine, Diagnosis and management of Silver–Russell syndrome: first international consensus statement, Nat. Rev. Endocrinol. 13 (2) (2017) 105–124.
dc.sourceD. Liu, Y. Wang, X.-A. Yang, D. Liu, De novo mutation of paternal IGF2 gene causing silver–russell syndrome in a sporadic patient, Front. Genet. 8 (2017).
dc.sourceK. Yamoto, H. Saitsu, N. Nakagawa, H. Nakajima, T. Hasegawa, Y. Fujisawa, M. Kagami, M. Fukami, T. Ogata, De novo IGF2 mutation on the paternal allele in a patient with Silver–Russell syndrome and ectrodactyly, Hum. Mutat. 38 (8) (2017) 953–958.
dc.sourceR.G.H. Lindeboom, F. Supek, B. Lehner, The rules and impact of nonsense-mediated mRNA decay in human cancers, Nat. Genet. 48 (10) (2016) 1112–1118.
dc.sourceG. Estrada-Gutierrez, R.E. Cappello, N. Mishra, R. Romero, J.F. Strauss, S.W. Walsh, Increased expression of matrix metalloproteinase-1 in systemic vessels of preeclamptic women: a critical mediator of vascular dysfunction, Am. J. Pathol. 178 (2011) 451–460.
dc.sourceW.H. Nugent, N. Mishra, J.F. Strauss III, S.W. Walsh, Matrix metalloproteinase 1 causes vasoconstriction and enhances vessel reactivity to angiotensin II via protease- activated receptor 1, Reprod. Sci. 23 (4) (2016) 542–548.
dc.sourceS. Espino, Y Sosa, A. Flores-Pliego, A. Espejel-Nuñez, D. Medina-Bastidas, F. Vadillo- Ortega, V. Zaga-Clavellina, G. Estrada-Gutierrez, New insights into the role of matrix metalloproteinases in preeclampsia, Int. J. Mol. Sci. 18 (2017).
dc.sourceI.M. Clark, T.E. Cawston, Fragments of human fibroblast collagenase: purification and characterisation, Matrix Suppl. 1 (1992) 73.
dc.sourceS. Iyer, R. Visse, H. Nagase, K.R. Acharya, Crystal structure of an active form of human MMP-1, J. Mol. Biol. 362 (1) (2006) 78–88.
dc.sourceH.S. Gammill, R. Chettier, A. Brewer, J.M. Roberts, R. Shree, E. Tsigas, K. Ward, Cardiomyopathy and preeclampsia: shared genetics? Circulation 138 (21) (2018) 2359–2366.
dc.sourceinstname:Universidad del Rosario
dc.sourcereponame:Repositorio Institucional EdocUR
dc.subjectbiomarcadores genéticos
dc.subjectSindrome HELLP
dc.subjectMedicina molecular
dc.subjectSecuenciación exoma completo
dc.titleIdentifying new potential genetic biomarkers for HELLP syndrome using massive parallel sequencing
dc.typemasterThesis


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