Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors
- Autores
- Poulton, Cathryn J.; Schot, Rachel; Kia, Sima Kheradmand; Jones Bernal, Marta Celina; Verheijen, Frans W.; Venselaar, Hanka; Y. de Wit, Marie Claire; Graaff, Esther de; Bertoli Avella, Aida M.; Mancini, Grazia M. S.
- Año de publicación
- 2011
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- We describe a syndrome of primary microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes in two unrelated consanguineous families with at least three affected children. Linkage analysis revealed a region on chromosome 18 with a significant LOD score of 4.3. In this area, two homozygous nonconserved missense mutations in immediate early response 3 interacting protein 1 (IER3IP1) were found in patients from both families. IER3IP1 is highly expressed in the fetal brain cortex and fetal pancreas and is thought to be involved in endoplasmic reticulum stress response. We reported one of these families previously in a paper on Wolcott-Rallison syndrome (WRS). WRS is characterized by increased apoptotic cell death as part of an uncontrolled unfolded protein response. Increased apoptosis has been shown to be a cause of microcephaly in animal models. An autopsy specimen from one patient showed increased apoptosis in the cerebral cortex and pancreas beta cells, implicating premature cell death as the pathogenetic mechanism. Both patient fibroblasts and control fibroblasts treated with siRNA specific for IER3IP1 showed an increased susceptibility to apoptotic cell death under stress conditions in comparison to controls. This directly implicates IER3IP1 in the regulation of cell survival. Identification of IER3IP1 mutations sheds light on the mechanisms of brain development and on the pathogenesis of infantile epilepsy and early-onset permanent diabetes.
Facultad de Ciencias Médicas - Materia
-
Ciencias Médicas
microcephaly
Epilepsy
Infantile Diabetes - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/83943
Ver los metadatos del registro completo
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Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitorsPoulton, Cathryn J.Schot, RachelKia, Sima KheradmandJones Bernal, Marta CelinaVerheijen, Frans W.Venselaar, HankaY. de Wit, Marie ClaireGraaff, Esther deBertoli Avella, Aida M.Mancini, Grazia M. S.Ciencias MédicasmicrocephalyEpilepsyInfantile DiabetesWe describe a syndrome of primary microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes in two unrelated consanguineous families with at least three affected children. Linkage analysis revealed a region on chromosome 18 with a significant LOD score of 4.3. In this area, two homozygous nonconserved missense mutations in immediate early response 3 interacting protein 1 (<i>IER3IP1</i>) were found in patients from both families. <i>IER3IP1</i> is highly expressed in the fetal brain cortex and fetal pancreas and is thought to be involved in endoplasmic reticulum stress response. We reported one of these families previously in a paper on Wolcott-Rallison syndrome (WRS). WRS is characterized by increased apoptotic cell death as part of an uncontrolled unfolded protein response. Increased apoptosis has been shown to be a cause of microcephaly in animal models. An autopsy specimen from one patient showed increased apoptosis in the cerebral cortex and pancreas beta cells, implicating premature cell death as the pathogenetic mechanism. Both patient fibroblasts and control fibroblasts treated with siRNA specific for <i>IER3IP1</i> showed an increased susceptibility to apoptotic cell death under stress conditions in comparison to controls. This directly implicates <i>IER3IP1</i> in the regulation of cell survival. Identification of <i>IER3IP1</i> mutations sheds light on the mechanisms of brain development and on the pathogenesis of infantile epilepsy and early-onset permanent diabetes.Facultad de Ciencias Médicas2011info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf265-276http://sedici.unlp.edu.ar/handle/10915/83943enginfo:eu-repo/semantics/altIdentifier/issn/0002-9297info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ajhg.2011.07.006info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:16:06Zoai:sedici.unlp.edu.ar:10915/83943Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:16:06.469SEDICI (UNLP) - Universidad Nacional de La Platafalse |
dc.title.none.fl_str_mv |
Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors |
title |
Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors |
spellingShingle |
Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors Poulton, Cathryn J. Ciencias Médicas microcephaly Epilepsy Infantile Diabetes |
title_short |
Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors |
title_full |
Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors |
title_fullStr |
Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors |
title_full_unstemmed |
Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors |
title_sort |
Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors |
dc.creator.none.fl_str_mv |
Poulton, Cathryn J. Schot, Rachel Kia, Sima Kheradmand Jones Bernal, Marta Celina Verheijen, Frans W. Venselaar, Hanka Y. de Wit, Marie Claire Graaff, Esther de Bertoli Avella, Aida M. Mancini, Grazia M. S. |
author |
Poulton, Cathryn J. |
author_facet |
Poulton, Cathryn J. Schot, Rachel Kia, Sima Kheradmand Jones Bernal, Marta Celina Verheijen, Frans W. Venselaar, Hanka Y. de Wit, Marie Claire Graaff, Esther de Bertoli Avella, Aida M. Mancini, Grazia M. S. |
author_role |
author |
author2 |
Schot, Rachel Kia, Sima Kheradmand Jones Bernal, Marta Celina Verheijen, Frans W. Venselaar, Hanka Y. de Wit, Marie Claire Graaff, Esther de Bertoli Avella, Aida M. Mancini, Grazia M. S. |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
Ciencias Médicas microcephaly Epilepsy Infantile Diabetes |
topic |
Ciencias Médicas microcephaly Epilepsy Infantile Diabetes |
dc.description.none.fl_txt_mv |
We describe a syndrome of primary microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes in two unrelated consanguineous families with at least three affected children. Linkage analysis revealed a region on chromosome 18 with a significant LOD score of 4.3. In this area, two homozygous nonconserved missense mutations in immediate early response 3 interacting protein 1 (<i>IER3IP1</i>) were found in patients from both families. <i>IER3IP1</i> is highly expressed in the fetal brain cortex and fetal pancreas and is thought to be involved in endoplasmic reticulum stress response. We reported one of these families previously in a paper on Wolcott-Rallison syndrome (WRS). WRS is characterized by increased apoptotic cell death as part of an uncontrolled unfolded protein response. Increased apoptosis has been shown to be a cause of microcephaly in animal models. An autopsy specimen from one patient showed increased apoptosis in the cerebral cortex and pancreas beta cells, implicating premature cell death as the pathogenetic mechanism. Both patient fibroblasts and control fibroblasts treated with siRNA specific for <i>IER3IP1</i> showed an increased susceptibility to apoptotic cell death under stress conditions in comparison to controls. This directly implicates <i>IER3IP1</i> in the regulation of cell survival. Identification of <i>IER3IP1</i> mutations sheds light on the mechanisms of brain development and on the pathogenesis of infantile epilepsy and early-onset permanent diabetes. Facultad de Ciencias Médicas |
description |
We describe a syndrome of primary microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes in two unrelated consanguineous families with at least three affected children. Linkage analysis revealed a region on chromosome 18 with a significant LOD score of 4.3. In this area, two homozygous nonconserved missense mutations in immediate early response 3 interacting protein 1 (<i>IER3IP1</i>) were found in patients from both families. <i>IER3IP1</i> is highly expressed in the fetal brain cortex and fetal pancreas and is thought to be involved in endoplasmic reticulum stress response. We reported one of these families previously in a paper on Wolcott-Rallison syndrome (WRS). WRS is characterized by increased apoptotic cell death as part of an uncontrolled unfolded protein response. Increased apoptosis has been shown to be a cause of microcephaly in animal models. An autopsy specimen from one patient showed increased apoptosis in the cerebral cortex and pancreas beta cells, implicating premature cell death as the pathogenetic mechanism. Both patient fibroblasts and control fibroblasts treated with siRNA specific for <i>IER3IP1</i> showed an increased susceptibility to apoptotic cell death under stress conditions in comparison to controls. This directly implicates <i>IER3IP1</i> in the regulation of cell survival. Identification of <i>IER3IP1</i> mutations sheds light on the mechanisms of brain development and on the pathogenesis of infantile epilepsy and early-onset permanent diabetes. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Articulo http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
status_str |
publishedVersion |
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http://sedici.unlp.edu.ar/handle/10915/83943 |
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http://sedici.unlp.edu.ar/handle/10915/83943 |
dc.language.none.fl_str_mv |
eng |
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eng |
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info:eu-repo/semantics/altIdentifier/issn/0002-9297 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ajhg.2011.07.006 |
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info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
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openAccess |
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http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
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