Protein S gene mutation c.946C > T (p.R316C) contributed to ischemic stroke in a man with von Willebrand disease type 3 caused by two novel VWF gene mutations, c.2328delT (p.A778Lfs* 23) and c.6521G > T (p.C2174F)
Abstract The risk factors for a family with VWD presenting with an ischemic stroke (IS) were explored. FVIII activity (FVIII:C), VWF antigen (VWF:Ag), and protein S activity were measured. Next generation sequencing (NGS) was performed targeting F8, F9, VWF, PROC, and PROS1. Sanger sequencing valida...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-08-01
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| Series: | Clinical Case Reports |
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| Online Access: | https://doi.org/10.1002/ccr3.6269 |
| _version_ | 1828431593782378496 |
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| author | Baolai Hua Xiaobo Yan Bin He Lianjun Shen Man‐Chiu Poon |
| author_facet | Baolai Hua Xiaobo Yan Bin He Lianjun Shen Man‐Chiu Poon |
| author_sort | Baolai Hua |
| collection | DOAJ |
| description | Abstract The risk factors for a family with VWD presenting with an ischemic stroke (IS) were explored. FVIII activity (FVIII:C), VWF antigen (VWF:Ag), and protein S activity were measured. Next generation sequencing (NGS) was performed targeting F8, F9, VWF, PROC, and PROS1. Sanger sequencing validation was performed on family members. The proband and his sister both had low FVIII:C (1 IU/dL) and VWF:Ag (3 IU/dL) levels, confirming the diagnosis of type 3 VWD. His father had nearly normal levels of FVIII:C (58 IU/dL) and VWF:Ag (57 IU/dL). His daughter had type 1 VWD with decreased FVIII:C (46 IU/dL) and VWF:Ag (19 IU/dL). NGS identified a heterozygous VWF c.2328delT (p.A778Lfs*23) frame shift mutation only in the proband and his sister. Another VWF missense mutation, c.6521G > T (p.C2174F), was found heterozygous in all members studied. A PROS1 mutation, c.946C > T (p.R316C), previously reported to relate to ischemic stroke, was found heterozygous in the patient, his father, and his daughter. Only the proband and daughter have a slightly decreased plasma protein S level. This may be the first case with type 3 VWD with severe VWF/FVIII deficiency presented with ischemic stroke contributed to by a protein S defect. |
| first_indexed | 2024-12-10T18:05:29Z |
| format | Article |
| id | doaj.art-f9eebffe393542d7a628569d4240b8ed |
| institution | Directory Open Access Journal |
| issn | 2050-0904 |
| language | English |
| last_indexed | 2024-12-10T18:05:29Z |
| publishDate | 2022-08-01 |
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| series | Clinical Case Reports |
| spelling | doaj.art-f9eebffe393542d7a628569d4240b8ed2022-12-22T01:38:37ZengWileyClinical Case Reports2050-09042022-08-01108n/an/a10.1002/ccr3.6269Protein S gene mutation c.946C > T (p.R316C) contributed to ischemic stroke in a man with von Willebrand disease type 3 caused by two novel VWF gene mutations, c.2328delT (p.A778Lfs* 23) and c.6521G > T (p.C2174F)Baolai Hua0Xiaobo Yan1Bin He2Lianjun Shen3Man‐Chiu Poon4Department of Hematology Beijing Shijitan Hospital, Capital Medical University Beijing ChinaDepartment of Hematology Yuebei People's Hospital affiliated to Medical College of Shantou University Shaoguan ChinaDepartment of Hematology Clinical Medical College, Yangzhou University Yangzhou ChinaDepartment of Hematology Clinical Medical College, Yangzhou University Yangzhou ChinaDepartment of Medicine University of Calgary, Cumming School of Medicine, Foothills Medical Center, and Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program Calgary CanadaAbstract The risk factors for a family with VWD presenting with an ischemic stroke (IS) were explored. FVIII activity (FVIII:C), VWF antigen (VWF:Ag), and protein S activity were measured. Next generation sequencing (NGS) was performed targeting F8, F9, VWF, PROC, and PROS1. Sanger sequencing validation was performed on family members. The proband and his sister both had low FVIII:C (1 IU/dL) and VWF:Ag (3 IU/dL) levels, confirming the diagnosis of type 3 VWD. His father had nearly normal levels of FVIII:C (58 IU/dL) and VWF:Ag (57 IU/dL). His daughter had type 1 VWD with decreased FVIII:C (46 IU/dL) and VWF:Ag (19 IU/dL). NGS identified a heterozygous VWF c.2328delT (p.A778Lfs*23) frame shift mutation only in the proband and his sister. Another VWF missense mutation, c.6521G > T (p.C2174F), was found heterozygous in all members studied. A PROS1 mutation, c.946C > T (p.R316C), previously reported to relate to ischemic stroke, was found heterozygous in the patient, his father, and his daughter. Only the proband and daughter have a slightly decreased plasma protein S level. This may be the first case with type 3 VWD with severe VWF/FVIII deficiency presented with ischemic stroke contributed to by a protein S defect.https://doi.org/10.1002/ccr3.6269gene mutationischemic stroke (IS)protein S (PS)von willebrand disease (VWD) |
| spellingShingle | Baolai Hua Xiaobo Yan Bin He Lianjun Shen Man‐Chiu Poon Protein S gene mutation c.946C > T (p.R316C) contributed to ischemic stroke in a man with von Willebrand disease type 3 caused by two novel VWF gene mutations, c.2328delT (p.A778Lfs* 23) and c.6521G > T (p.C2174F) Clinical Case Reports gene mutation ischemic stroke (IS) protein S (PS) von willebrand disease (VWD) |
| title | Protein S gene mutation c.946C > T (p.R316C) contributed to ischemic stroke in a man with von Willebrand disease type 3 caused by two novel VWF gene mutations, c.2328delT (p.A778Lfs* 23) and c.6521G > T (p.C2174F) |
| title_full | Protein S gene mutation c.946C > T (p.R316C) contributed to ischemic stroke in a man with von Willebrand disease type 3 caused by two novel VWF gene mutations, c.2328delT (p.A778Lfs* 23) and c.6521G > T (p.C2174F) |
| title_fullStr | Protein S gene mutation c.946C > T (p.R316C) contributed to ischemic stroke in a man with von Willebrand disease type 3 caused by two novel VWF gene mutations, c.2328delT (p.A778Lfs* 23) and c.6521G > T (p.C2174F) |
| title_full_unstemmed | Protein S gene mutation c.946C > T (p.R316C) contributed to ischemic stroke in a man with von Willebrand disease type 3 caused by two novel VWF gene mutations, c.2328delT (p.A778Lfs* 23) and c.6521G > T (p.C2174F) |
| title_short | Protein S gene mutation c.946C > T (p.R316C) contributed to ischemic stroke in a man with von Willebrand disease type 3 caused by two novel VWF gene mutations, c.2328delT (p.A778Lfs* 23) and c.6521G > T (p.C2174F) |
| title_sort | protein s gene mutation c 946c t p r316c contributed to ischemic stroke in a man with von willebrand disease type 3 caused by two novel vwf gene mutations c 2328delt p a778lfs 23 and c 6521g t p c2174f |
| topic | gene mutation ischemic stroke (IS) protein S (PS) von willebrand disease (VWD) |
| url | https://doi.org/10.1002/ccr3.6269 |
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