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A Novel PKD1 Mutation Associated With Autosomal Dominant Kidney Disease and Cerebral Cavernous Malformation

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the presence of renal cysts and specific extrarenal abnormalities. ADPKD is caused by mutations in either PKD1 or PKD2 genes that encode for integral membrane proteins Polycystin-1 (PC1) and Polycystin-2 (PC2...

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Autores principales: Thomas, Christian, Zühlsdorf, Andrea, Hörtnagel, Konstanze, Mulahasanovic, Lejla, Grauer, Oliver M., Kümpers, Philipp, Wiendl, Heinz, Meuth, Sven G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980969/
https://www.ncbi.nlm.nih.gov/pubmed/29887830
http://dx.doi.org/10.3389/fneur.2018.00383
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author Thomas, Christian
Zühlsdorf, Andrea
Hörtnagel, Konstanze
Mulahasanovic, Lejla
Grauer, Oliver M.
Kümpers, Philipp
Wiendl, Heinz
Meuth, Sven G.
author_facet Thomas, Christian
Zühlsdorf, Andrea
Hörtnagel, Konstanze
Mulahasanovic, Lejla
Grauer, Oliver M.
Kümpers, Philipp
Wiendl, Heinz
Meuth, Sven G.
author_sort Thomas, Christian
collection PubMed
description Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the presence of renal cysts and specific extrarenal abnormalities. ADPKD is caused by mutations in either PKD1 or PKD2 genes that encode for integral membrane proteins Polycystin-1 (PC1) and Polycystin-2 (PC2), respectively. Extrarenal involvement includes noncystic manifestations such as dilatation of the aortic root, artery dissection and intracranial aneurysms. Cerebral cavernous malformation (CCM) is a rare vascular malformation disorder characterized by closely clustered and irregularly dilated capillaries that can be asymptomatic or cause variable neurological manifestations, such as seizures, non-specific headaches, progressive or transient focal neurologic deficits, and cerebral hemorrhages. Familial CCM is typically associated with mutations in KRIT1 (CCM1), CCM2, and PDCD10 (CCM3). The co-occurrence of ADPKD and CCM has been previously described in a single patient, although genetic analysis was not performed in this study. We report here a family with ADPKD associated with CCM in two sisters. Direct sequencing of the index patient revealed a single novel heterozygous frameshift mutation in PKD1, and lack of mutations in genes usually related to CCM. This suggests that CCM represents an additional phenotype of ADPKD.
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spelling pubmed-59809692018-06-08 A Novel PKD1 Mutation Associated With Autosomal Dominant Kidney Disease and Cerebral Cavernous Malformation Thomas, Christian Zühlsdorf, Andrea Hörtnagel, Konstanze Mulahasanovic, Lejla Grauer, Oliver M. Kümpers, Philipp Wiendl, Heinz Meuth, Sven G. Front Neurol Neurology Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the presence of renal cysts and specific extrarenal abnormalities. ADPKD is caused by mutations in either PKD1 or PKD2 genes that encode for integral membrane proteins Polycystin-1 (PC1) and Polycystin-2 (PC2), respectively. Extrarenal involvement includes noncystic manifestations such as dilatation of the aortic root, artery dissection and intracranial aneurysms. Cerebral cavernous malformation (CCM) is a rare vascular malformation disorder characterized by closely clustered and irregularly dilated capillaries that can be asymptomatic or cause variable neurological manifestations, such as seizures, non-specific headaches, progressive or transient focal neurologic deficits, and cerebral hemorrhages. Familial CCM is typically associated with mutations in KRIT1 (CCM1), CCM2, and PDCD10 (CCM3). The co-occurrence of ADPKD and CCM has been previously described in a single patient, although genetic analysis was not performed in this study. We report here a family with ADPKD associated with CCM in two sisters. Direct sequencing of the index patient revealed a single novel heterozygous frameshift mutation in PKD1, and lack of mutations in genes usually related to CCM. This suggests that CCM represents an additional phenotype of ADPKD. Frontiers Media S.A. 2018-05-25 /pmc/articles/PMC5980969/ /pubmed/29887830 http://dx.doi.org/10.3389/fneur.2018.00383 Text en Copyright © 2018 Thomas, Zühlsdorf, Hörtnagel, Mulahasanovic, Grauer, Kümpers, Wiendl and Meuth. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Thomas, Christian
Zühlsdorf, Andrea
Hörtnagel, Konstanze
Mulahasanovic, Lejla
Grauer, Oliver M.
Kümpers, Philipp
Wiendl, Heinz
Meuth, Sven G.
A Novel PKD1 Mutation Associated With Autosomal Dominant Kidney Disease and Cerebral Cavernous Malformation
title A Novel PKD1 Mutation Associated With Autosomal Dominant Kidney Disease and Cerebral Cavernous Malformation
title_full A Novel PKD1 Mutation Associated With Autosomal Dominant Kidney Disease and Cerebral Cavernous Malformation
title_fullStr A Novel PKD1 Mutation Associated With Autosomal Dominant Kidney Disease and Cerebral Cavernous Malformation
title_full_unstemmed A Novel PKD1 Mutation Associated With Autosomal Dominant Kidney Disease and Cerebral Cavernous Malformation
title_short A Novel PKD1 Mutation Associated With Autosomal Dominant Kidney Disease and Cerebral Cavernous Malformation
title_sort novel pkd1 mutation associated with autosomal dominant kidney disease and cerebral cavernous malformation
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980969/
https://www.ncbi.nlm.nih.gov/pubmed/29887830
http://dx.doi.org/10.3389/fneur.2018.00383
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