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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-05-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2018.00383/full |
| _version_ | 1811231486197628928 |
|---|---|
| author | Christian Thomas Andrea Zühlsdorf Konstanze Hörtnagel Lejla Mulahasanovic Oliver M. Grauer Philipp Kümpers Heinz Wiendl Sven G. Meuth |
| author_facet | Christian Thomas Andrea Zühlsdorf Konstanze Hörtnagel Lejla Mulahasanovic Oliver M. Grauer Philipp Kümpers Heinz Wiendl Sven G. Meuth |
| author_sort | Christian Thomas |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T10:46:08Z |
| format | Article |
| id | doaj.art-e04731d0c73d491ab68b05814a86a46b |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-12T10:46:08Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-e04731d0c73d491ab68b05814a86a46b2022-12-22T03:36:25ZengFrontiers Media S.A.Frontiers in Neurology1664-22952018-05-01910.3389/fneur.2018.00383379146A Novel PKD1 Mutation Associated With Autosomal Dominant Kidney Disease and Cerebral Cavernous MalformationChristian Thomas0Andrea Zühlsdorf1Konstanze Hörtnagel2Lejla Mulahasanovic3Oliver M. Grauer4Philipp Kümpers5Heinz Wiendl6Sven G. Meuth7Clinic of Neurology with Institute of Translational Neurology, University of Münster, Münster, GermanyDepartment of General Pediatrics, Metabolic Diseases, University Children's Hospital Münster, Münster, GermanyCeGaT GmbH and Praxis für Humangenetik Tübingen, Tübingen, GermanyCeGaT GmbH and Praxis für Humangenetik Tübingen, Tübingen, GermanyClinic of Neurology with Institute of Translational Neurology, University of Münster, Münster, GermanyDivision of General Internal Medicine, Nephrology, and Rheumatology, Department of Medicine D, University Hospital Münster, Münster, GermanyClinic of Neurology with Institute of Translational Neurology, University of Münster, Münster, GermanyClinic of Neurology with Institute of Translational Neurology, University of Münster, Münster, GermanyAutosomal 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.https://www.frontiersin.org/article/10.3389/fneur.2018.00383/fullADPKDCCMsequencingfamilialmutation |
| spellingShingle | Christian Thomas Andrea Zühlsdorf Konstanze Hörtnagel Lejla Mulahasanovic Oliver M. Grauer Philipp Kümpers Heinz Wiendl Sven G. Meuth A Novel PKD1 Mutation Associated With Autosomal Dominant Kidney Disease and Cerebral Cavernous Malformation Frontiers in Neurology ADPKD CCM sequencing familial mutation |
| 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 | ADPKD CCM sequencing familial mutation |
| url | https://www.frontiersin.org/article/10.3389/fneur.2018.00383/full |
| work_keys_str_mv | AT christianthomas anovelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT andreazuhlsdorf anovelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT konstanzehortnagel anovelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT lejlamulahasanovic anovelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT olivermgrauer anovelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT philippkumpers anovelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT heinzwiendl anovelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT svengmeuth anovelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT christianthomas novelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT andreazuhlsdorf novelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT konstanzehortnagel novelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT lejlamulahasanovic novelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT olivermgrauer novelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT philippkumpers novelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT heinzwiendl novelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation AT svengmeuth novelpkd1mutationassociatedwithautosomaldominantkidneydiseaseandcerebralcavernousmalformation |