TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients
Authors
Foddis, MarcoBlumenau, Sonja
Holtgrewe, Manuel
Paquette, Kimberly
Westra, Kaitlyn
Alonso, Isabel
Macario, Maria do Carmo
Morgadinho, Ana Sofia
Velon, Ana Graça
Santo, Gustavo
Santana, Isabel
Mönkäre, Saana
Kuuluvainen, Liina
Schleutker, Johanna
Pöyhönen, Minna
Myllykangas, Liisa
Pavlović, Aleksandra

Kostic, Vladimir
Dobricic, Valerija
Lohmann, Ebba
Hanagasi, Hasmet
Santos, Mariana
Guven, Gamze
Bilgic, Basar
Bras, Jose
Beule, Dieter
Dirnagl, Ulrich
Guerreiro, Rita
Sassi, Celeste
Article (Published version)
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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) are the most common forms of rare monogenic early-onset cerebral small vessel disease and share clinical, and, to different extents, neuroradiological and neuropathological features. However, whether CADASIL and RVCL-S overlapping phenotype may be explained by shared genetic risk or causative factors such as TREX1 coding variants remains poorly understood. To investigate this intriguing hypothesis, we used exome sequencing to screen TREX1 protein-coding variability in a large multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic CADASIL-like Caucasian patients from the USA, Portugal, Finland, Serbia and Turkey. We report 2 very rare and likely pathogenic TREX1 mutations: a loss of function mutation (p.Ala129fs) clustering in the catalytic domain, in an apparently spor...adic 46-year-old patient from the USA and a missense mutation (p.Tyr305Cys) in the well conserved C-terminal region, in a 57-year-old patient with positive family history from Serbia. In concert with recent findings, our study expands the clinical spectrum of diseases associated with TREX1 mutations.
Keywords:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) / Early-onset stroke / Exome sequencing / retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S )Source:
Neurobiology of Aging, 2023, 123, 208-215Publisher:
- Elsevier
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https://www.sciencedirect.com/science/article/pii/S0197458022002433http://rfasper.fasper.bg.ac.rs/handle/123456789/5020
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rFASPERTY - JOUR AU - Foddis, Marco AU - Blumenau, Sonja AU - Holtgrewe, Manuel AU - Paquette, Kimberly AU - Westra, Kaitlyn AU - Alonso, Isabel AU - Macario, Maria do Carmo AU - Morgadinho, Ana Sofia AU - Velon, Ana Graça AU - Santo, Gustavo AU - Santana, Isabel AU - Mönkäre, Saana AU - Kuuluvainen, Liina AU - Schleutker, Johanna AU - Pöyhönen, Minna AU - Myllykangas, Liisa AU - Pavlović, Aleksandra AU - Kostic, Vladimir AU - Dobricic, Valerija AU - Lohmann, Ebba AU - Hanagasi, Hasmet AU - Santos, Mariana AU - Guven, Gamze AU - Bilgic, Basar AU - Bras, Jose AU - Beule, Dieter AU - Dirnagl, Ulrich AU - Guerreiro, Rita AU - Sassi, Celeste PY - 2023 PY - 2023 UR - https://www.sciencedirect.com/science/article/pii/S0197458022002433 UR - http://rfasper.fasper.bg.ac.rs/handle/123456789/5020 AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) are the most common forms of rare monogenic early-onset cerebral small vessel disease and share clinical, and, to different extents, neuroradiological and neuropathological features. However, whether CADASIL and RVCL-S overlapping phenotype may be explained by shared genetic risk or causative factors such as TREX1 coding variants remains poorly understood. To investigate this intriguing hypothesis, we used exome sequencing to screen TREX1 protein-coding variability in a large multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic CADASIL-like Caucasian patients from the USA, Portugal, Finland, Serbia and Turkey. We report 2 very rare and likely pathogenic TREX1 mutations: a loss of function mutation (p.Ala129fs) clustering in the catalytic domain, in an apparently sporadic 46-year-old patient from the USA and a missense mutation (p.Tyr305Cys) in the well conserved C-terminal region, in a 57-year-old patient with positive family history from Serbia. In concert with recent findings, our study expands the clinical spectrum of diseases associated with TREX1 mutations. PB - Elsevier T2 - Neurobiology of Aging T1 - TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients EP - 215 SP - 208 VL - 123 DO - 10.1016/j.neurobiolaging.2022.11.013 ER -
@article{ author = "Foddis, Marco and Blumenau, Sonja and Holtgrewe, Manuel and Paquette, Kimberly and Westra, Kaitlyn and Alonso, Isabel and Macario, Maria do Carmo and Morgadinho, Ana Sofia and Velon, Ana Graça and Santo, Gustavo and Santana, Isabel and Mönkäre, Saana and Kuuluvainen, Liina and Schleutker, Johanna and Pöyhönen, Minna and Myllykangas, Liisa and Pavlović, Aleksandra and Kostic, Vladimir and Dobricic, Valerija and Lohmann, Ebba and Hanagasi, Hasmet and Santos, Mariana and Guven, Gamze and Bilgic, Basar and Bras, Jose and Beule, Dieter and Dirnagl, Ulrich and Guerreiro, Rita and Sassi, Celeste", year = "2023, 2023", abstract = "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) are the most common forms of rare monogenic early-onset cerebral small vessel disease and share clinical, and, to different extents, neuroradiological and neuropathological features. However, whether CADASIL and RVCL-S overlapping phenotype may be explained by shared genetic risk or causative factors such as TREX1 coding variants remains poorly understood. To investigate this intriguing hypothesis, we used exome sequencing to screen TREX1 protein-coding variability in a large multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic CADASIL-like Caucasian patients from the USA, Portugal, Finland, Serbia and Turkey. We report 2 very rare and likely pathogenic TREX1 mutations: a loss of function mutation (p.Ala129fs) clustering in the catalytic domain, in an apparently sporadic 46-year-old patient from the USA and a missense mutation (p.Tyr305Cys) in the well conserved C-terminal region, in a 57-year-old patient with positive family history from Serbia. In concert with recent findings, our study expands the clinical spectrum of diseases associated with TREX1 mutations.", publisher = "Elsevier", journal = "Neurobiology of Aging", title = "TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients", pages = "215-208", volume = "123", doi = "10.1016/j.neurobiolaging.2022.11.013" }
Foddis, M., Blumenau, S., Holtgrewe, M., Paquette, K., Westra, K., Alonso, I., Macario, M. d. C., Morgadinho, A. S., Velon, A. G., Santo, G., Santana, I., Mönkäre, S., Kuuluvainen, L., Schleutker, J., Pöyhönen, M., Myllykangas, L., Pavlović, A., Kostic, V., Dobricic, V., Lohmann, E., Hanagasi, H., Santos, M., Guven, G., Bilgic, B., Bras, J., Beule, D., Dirnagl, U., Guerreiro, R.,& Sassi, C.. (2023). TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients. in Neurobiology of Aging Elsevier., 123, 208-215. https://doi.org/10.1016/j.neurobiolaging.2022.11.013
Foddis M, Blumenau S, Holtgrewe M, Paquette K, Westra K, Alonso I, Macario MDC, Morgadinho AS, Velon AG, Santo G, Santana I, Mönkäre S, Kuuluvainen L, Schleutker J, Pöyhönen M, Myllykangas L, Pavlović A, Kostic V, Dobricic V, Lohmann E, Hanagasi H, Santos M, Guven G, Bilgic B, Bras J, Beule D, Dirnagl U, Guerreiro R, Sassi C. TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients. in Neurobiology of Aging. 2023;123:208-215. doi:10.1016/j.neurobiolaging.2022.11.013 .
Foddis, Marco, Blumenau, Sonja, Holtgrewe, Manuel, Paquette, Kimberly, Westra, Kaitlyn, Alonso, Isabel, Macario, Maria do Carmo, Morgadinho, Ana Sofia, Velon, Ana Graça, Santo, Gustavo, Santana, Isabel, Mönkäre, Saana, Kuuluvainen, Liina, Schleutker, Johanna, Pöyhönen, Minna, Myllykangas, Liisa, Pavlović, Aleksandra, Kostic, Vladimir, Dobricic, Valerija, Lohmann, Ebba, Hanagasi, Hasmet, Santos, Mariana, Guven, Gamze, Bilgic, Basar, Bras, Jose, Beule, Dieter, Dirnagl, Ulrich, Guerreiro, Rita, Sassi, Celeste, "TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients" in Neurobiology of Aging, 123 (2023):208-215, https://doi.org/10.1016/j.neurobiolaging.2022.11.013 . .