Genetic analysis of a family presenting with coexisting cerebral cavernous malformations and polycystic kidney disease
Hereditary cerebral cavernous malformations (CCMs) are characterized by clustered dilated capillary-like vessels in the brain. Autosomal dominant polycystic kidney disease (PKD) is characterized by renal cysts and extra-renal abnormalities. We report a Taiwanese family in which the index case exhibi...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Journal of the Formosan Medical Association |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0929664622001127 |
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| author | Pei-Feng Hsieh Shih-Yao Liu Chih-Hao Chen Pei-Lung Chen Sung-Chun Tang Jiann-Shing Jeng |
| author_facet | Pei-Feng Hsieh Shih-Yao Liu Chih-Hao Chen Pei-Lung Chen Sung-Chun Tang Jiann-Shing Jeng |
| author_sort | Pei-Feng Hsieh |
| collection | DOAJ |
| description | Hereditary cerebral cavernous malformations (CCMs) are characterized by clustered dilated capillary-like vessels in the brain. Autosomal dominant polycystic kidney disease (PKD) is characterized by renal cysts and extra-renal abnormalities. We report a Taiwanese family in which the index case exhibited coexisting phenotypes of both CCMs and PKD. The index case was a 55-year-old woman with known PKD who developed an intracerebral hemorrhage (ICH) in the right medulla. Neuroimaging revealed numerous microbleeds in the bilateral cerebrum and cerebellum. Radiological CCMs were suspected given the absence of other imaging markers of small vessel disease. A comprehensive panel of 183 cerebral vascular malformation genes were investigated through genome sequencing. A novel CCM2 frameshift variant (c.607_608delCT, p.Leu203Valfs∗53) causing a pathogenic premature stop codon, and a known PKD2 nonsense variant (c.2407C > T, p.Arg803∗), were found. Segregation analysis revealed that four siblings were affected by either isolated aforementioned PKD2 or CCM2 variant. Notably, radiological CCMs were exclusively found in siblings who had this CCM2 variant, and bilateral internal carotid artery aneurysms were restricted to one sibling who had the PKD2 variant but not the CCM2 variant. Our study expands the genetic spectrum of CCM2 and demonstrates unambiguous cosegregation of CCM2 and PKD2 variants with their respective phenotypes. |
| first_indexed | 2024-04-13T23:31:56Z |
| format | Article |
| id | doaj.art-b91ed3e08a014a029aa359db7635c6c7 |
| institution | Directory Open Access Journal |
| issn | 0929-6646 |
| language | English |
| last_indexed | 2024-04-13T23:31:56Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of the Formosan Medical Association |
| spelling | doaj.art-b91ed3e08a014a029aa359db7635c6c72022-12-22T02:24:52ZengElsevierJournal of the Formosan Medical Association0929-66462022-11-011211123312337Genetic analysis of a family presenting with coexisting cerebral cavernous malformations and polycystic kidney diseasePei-Feng Hsieh0Shih-Yao Liu1Chih-Hao Chen2Pei-Lung Chen3Sung-Chun Tang4Jiann-Shing Jeng5Department of Neurology, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, TaiwanDepartment of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Corresponding author. Department of Neurology, National Taiwan University Hospital, No. 7, Chungshan South Road, Taipei, 100, Taiwan.Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, TaiwanDepartment of Neurology, National Taiwan University Hospital, Taipei, TaiwanDepartment of Neurology, National Taiwan University Hospital, Taipei, TaiwanHereditary cerebral cavernous malformations (CCMs) are characterized by clustered dilated capillary-like vessels in the brain. Autosomal dominant polycystic kidney disease (PKD) is characterized by renal cysts and extra-renal abnormalities. We report a Taiwanese family in which the index case exhibited coexisting phenotypes of both CCMs and PKD. The index case was a 55-year-old woman with known PKD who developed an intracerebral hemorrhage (ICH) in the right medulla. Neuroimaging revealed numerous microbleeds in the bilateral cerebrum and cerebellum. Radiological CCMs were suspected given the absence of other imaging markers of small vessel disease. A comprehensive panel of 183 cerebral vascular malformation genes were investigated through genome sequencing. A novel CCM2 frameshift variant (c.607_608delCT, p.Leu203Valfs∗53) causing a pathogenic premature stop codon, and a known PKD2 nonsense variant (c.2407C > T, p.Arg803∗), were found. Segregation analysis revealed that four siblings were affected by either isolated aforementioned PKD2 or CCM2 variant. Notably, radiological CCMs were exclusively found in siblings who had this CCM2 variant, and bilateral internal carotid artery aneurysms were restricted to one sibling who had the PKD2 variant but not the CCM2 variant. Our study expands the genetic spectrum of CCM2 and demonstrates unambiguous cosegregation of CCM2 and PKD2 variants with their respective phenotypes.http://www.sciencedirect.com/science/article/pii/S0929664622001127CCM2PKD2Cerebral cavernous malformationsPolycystic kidney disease |
| spellingShingle | Pei-Feng Hsieh Shih-Yao Liu Chih-Hao Chen Pei-Lung Chen Sung-Chun Tang Jiann-Shing Jeng Genetic analysis of a family presenting with coexisting cerebral cavernous malformations and polycystic kidney disease Journal of the Formosan Medical Association CCM2 PKD2 Cerebral cavernous malformations Polycystic kidney disease |
| title | Genetic analysis of a family presenting with coexisting cerebral cavernous malformations and polycystic kidney disease |
| title_full | Genetic analysis of a family presenting with coexisting cerebral cavernous malformations and polycystic kidney disease |
| title_fullStr | Genetic analysis of a family presenting with coexisting cerebral cavernous malformations and polycystic kidney disease |
| title_full_unstemmed | Genetic analysis of a family presenting with coexisting cerebral cavernous malformations and polycystic kidney disease |
| title_short | Genetic analysis of a family presenting with coexisting cerebral cavernous malformations and polycystic kidney disease |
| title_sort | genetic analysis of a family presenting with coexisting cerebral cavernous malformations and polycystic kidney disease |
| topic | CCM2 PKD2 Cerebral cavernous malformations Polycystic kidney disease |
| url | http://www.sciencedirect.com/science/article/pii/S0929664622001127 |
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