Polyhydramnios, Transient Antenatal Bartter's Syndrome, and MAGED2 Mutations
| Autor: | Christoph J. Mache, Bodo B. Beck, Malte P. Bartram, Janine Altmüller, Thomas Benzing, L. K. Duin, Mathieu J.M. Bertrand, Markus M. Rinschen, Sung Sen Yang, Sicco A. Scherjon, Kamel Laghmani, Olivier De Backer, Tom J. de Koning, Björn Reusch, Holger Thiele, Shih-Hua Lin, Sylvie Demaretz, Hannsjörg W. Seyberth, Karl P. Schlingmann, Elena Levtchenko, Albert Timmer, Günter Klaus, Heike Göbel, Gökhan Yigit, Andrea Wenzel, Martin Kömhoff, Carlos Dombret, Elie Seaayfan, Helga Vitzthum, Klasien Bergmann, Martin Konrad, Dario Priem, Peter Nürnberg |
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| Přispěvatelé: | Reproductive Origins of Adult Health and Disease (ROAHD), Movement Disorder (MD) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
EXPRESSION medicine.medical_specialty Polyhydramnios Offspring NEPHRON 030232 urology & nephrology HYPOXIA Bartter syndrome DISEASE 03 medical and health sciences 0302 clinical medicine Polyuria Internal medicine medicine PREGNANCIES RECURRENT X chromosome Obstetrics business.industry AMNIOCENTESES ADENYLATE-CYCLASE Kidney metabolism General Medicine DEGRADATION medicine.disease Bartter's syndrome COTRANSPORTER 030104 developmental biology Endocrinology Medical genetics medicine.symptom business |
| Zdroj: | Laghmani, K, Beck, B B, Yang, S S, Seaayfan, E, Wenzel, A, Reusch, B, Vitzthum, H, Priem, D, Demaretz, S, Bergmann, K, Duin, L K, Gobel, H, Mache, C, Thiele, H, Bartram, M P, Dombret, C, Altmuller, J, Nurnberg, P, Benzing, T, Levtchenko, E, Seyberth, H W, Klaus, G, Yigit, G, Lin, S H, Timmer, A, De Koning, T J, Scherjon, S A, Schlingmann, K P, Bertrand, M J M, Rinschen, M M, De Backer, O, Konrad, M & Komhoff, M 2016, ' Polyhydramnios, transient antenatal bartter's syndrome, and MAGED2 mutations ', New England Journal of Medicine, vol. 374, no. 19, pp. 1853-1863 . https://doi.org/10.1056/NEJMoa1507629 New England Journal of Medicine, 374(19), 1853-1863. MASSACHUSETTS MEDICAL SOC |
| ISSN: | 1533-4406 0028-4793 |
| Popis: | Background Three pregnancies with male offspring in one family were complicated by severe polyhydramnios and prematurity. One fetus died; the other two had transient massive salt-wasting and polyuria reminiscent of antenatal Bartter's syndrome. Methods To uncover the molecular cause of this possibly X-linked disease, we performed whole-exome sequencing of DNA from two members of the index family and targeted gene analysis of other members of this family and of six additional families with affected male fetuses. We also evaluated a series of women with idiopathic polyhydramnios who were pregnant with male fetuses. We performed immunohistochemical analysis, knockdown and overexpression experiments, and protein-protein interaction studies. Results We identified a mutation in MAGED2 in each of the 13 infants in our analysis who had transient antenatal Bartter's syndrome. MAGED2 encodes melanoma-associated antigen D2 (MAGE-D2) and maps to the X chromosome. We also identified two different MAGED2 mutations in two families with idiopathic polyhydramnios. Four patients died perinatally, and 11 survived. The initial presentation was more severe than in known types of antenatal Bartter's syndrome, as reflected by an earlier onset of polyhydramnios and labor. All symptoms disappeared spontaneously during follow-up in the infants who survived. We showed that MAGE-D2 affects the expression and function of the sodium chloride cotransporters NKCC2 and NCC (key components of salt reabsorption in the distal renal tubule), possibly through adenylate cyclase and cyclic AMP signaling and a cytoplasmic heat-shock protein. Conclusions We found that MAGED2 mutations caused X-linked polyhydramnios with prematurity and a severe but transient form of antenatal Bartter's syndrome. MAGE-D2 is essential for fetal renal salt reabsorption, amniotic fluid homeostasis, and the maintenance of pregnancy. (Funded by the University of Groningen and others.). |
| Databáze: | OpenAIRE |
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