TY  - 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 . .

TY  - JOUR
AU  - Messerschmidt, Clemens
AU  - Foddis, Marco
AU  - Blumenau, Sonja
AU  - Müller, Susanne
AU  - Bentele, Kajetan
AU  - Holtgrewe, Manuel
AU  - Kun-Rodrigues, Celia
AU  - Alonso, Isabel
AU  - do Carmo Macario, Maria
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  - Senatore, Assunta
AU  - Berchtold, Daniel
AU  - Winek, Katarzyna
AU  - Meisel, Andreas
AU  - Pavlović, Aleksandra
AU  - Kostić, Vladimir
AU  - Dobricic, Valerija
AU  - Lohmann, Ebba
AU  - Hanagasi, Hasmet
AU  - Guven, Gamze
AU  - Bilgic, Basar
AU  - Bras, Jose
AU  - Guerreiro, Rita
AU  - Beule, Dieter
AU  - Dirnagl, Ulrich
AU  - Sassi, Celeste
PY  - 2021
PY  - 2021
UR  - https://www.nature.com/articles/s41598-021-84919-x
UR  - http://rfasper.fasper.bg.ac.rs/handle/123456789/5024
AB  - Recently, several genome-wide association studies identified PHACTR1 as key locus for five diverse vascular disorders: coronary artery disease, migraine, fibromuscular dysplasia, cervical artery dissection and hypertension. Although these represent significant risk factors or comorbidities for ischemic stroke, PHACTR1 role in brain small vessel ischemic disease and ischemic stroke most important survival mechanism, such as the recruitment of brain collateral arteries like posterior communicating arteries (PcomAs), remains unknown. Therefore, we applied exome and genome sequencing in a multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic brain small vessel ischemic disease and CADASIL-like Caucasian patients from US, Portugal, Finland, Serbia and Turkey and in 2 C57BL/6J stroke mouse models (bilateral common carotid artery stenosis [BCCAS] and middle cerebral artery occlusion [MCAO]), characterized by different degrees of PcomAs patency. We report 3 very rare coding variants in the small vessel ischemic disease-CADASIL-like cohort (p.Glu198Gln, p.Arg204Gly, p.Val251Leu) and a stop-gain mutation (p.Gln273*) in one MCAO mouse. These coding variants do not cluster in PHACTR1 known pathogenic domains and are not likely to play a critical role in small vessel ischemic disease or brain collateral circulation. We also exclude the possibility that copy number variants (CNVs) or a variant enrichment in Phactr1 may be associated with PcomA recruitment in BCCAS mice or linked to diverse vascular traits (cerebral blood flow pre-surgery, PcomA size, leptomeningeal microcollateral length and junction density during brain hypoperfusion) in C57BL/6J mice, respectively. Genetic variability in PHACTR1 is not likely to be a common susceptibility factor influencing small vessel ischemic disease in patients and PcomA recruitment in C57BL/6J mice. Nonetheless, rare variants in PHACTR1 RPEL domains may influence the stroke outcome and are worth investigating in a larger cohort of small vessel ischemic disease patients, different ischemic stroke subtypes and with functional studies.
PB  - Nature Research
T2  - Scientific Reports
T1  - PHACTR1 genetic variability is not critical in small vessel ischemic disease patients and PcomA recruitment in C57BL/6J mice
IS  - 1
SP  - 6072
VL  - 11
DO  - 10.1038/s41598-021-84919-x
ER  - 

@article{
author = "Messerschmidt, Clemens and Foddis, Marco and Blumenau, Sonja and Müller, Susanne and Bentele, Kajetan and Holtgrewe, Manuel and Kun-Rodrigues, Celia and Alonso, Isabel and do Carmo Macario, Maria 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 Senatore, Assunta and Berchtold, Daniel and Winek, Katarzyna and Meisel, Andreas and Pavlović, Aleksandra and Kostić, Vladimir and Dobricic, Valerija and Lohmann, Ebba and Hanagasi, Hasmet and Guven, Gamze and Bilgic, Basar and Bras, Jose and Guerreiro, Rita and Beule, Dieter and Dirnagl, Ulrich and Sassi, Celeste",
year = "2021, 2021",
abstract = "Recently, several genome-wide association studies identified PHACTR1 as key locus for five diverse vascular disorders: coronary artery disease, migraine, fibromuscular dysplasia, cervical artery dissection and hypertension. Although these represent significant risk factors or comorbidities for ischemic stroke, PHACTR1 role in brain small vessel ischemic disease and ischemic stroke most important survival mechanism, such as the recruitment of brain collateral arteries like posterior communicating arteries (PcomAs), remains unknown. Therefore, we applied exome and genome sequencing in a multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic brain small vessel ischemic disease and CADASIL-like Caucasian patients from US, Portugal, Finland, Serbia and Turkey and in 2 C57BL/6J stroke mouse models (bilateral common carotid artery stenosis [BCCAS] and middle cerebral artery occlusion [MCAO]), characterized by different degrees of PcomAs patency. We report 3 very rare coding variants in the small vessel ischemic disease-CADASIL-like cohort (p.Glu198Gln, p.Arg204Gly, p.Val251Leu) and a stop-gain mutation (p.Gln273*) in one MCAO mouse. These coding variants do not cluster in PHACTR1 known pathogenic domains and are not likely to play a critical role in small vessel ischemic disease or brain collateral circulation. We also exclude the possibility that copy number variants (CNVs) or a variant enrichment in Phactr1 may be associated with PcomA recruitment in BCCAS mice or linked to diverse vascular traits (cerebral blood flow pre-surgery, PcomA size, leptomeningeal microcollateral length and junction density during brain hypoperfusion) in C57BL/6J mice, respectively. Genetic variability in PHACTR1 is not likely to be a common susceptibility factor influencing small vessel ischemic disease in patients and PcomA recruitment in C57BL/6J mice. Nonetheless, rare variants in PHACTR1 RPEL domains may influence the stroke outcome and are worth investigating in a larger cohort of small vessel ischemic disease patients, different ischemic stroke subtypes and with functional studies.",
publisher = "Nature Research",
journal = "Scientific Reports",
title = "PHACTR1 genetic variability is not critical in small vessel ischemic disease patients and PcomA recruitment in C57BL/6J mice",
number = "1",
pages = "6072",
volume = "11",
doi = "10.1038/s41598-021-84919-x"
}

Messerschmidt, C., Foddis, M., Blumenau, S., Müller, S., Bentele, K., Holtgrewe, M., Kun-Rodrigues, C., Alonso, I., do Carmo Macario, M., Morgadinho, A. S., Velon, A. G., Santo, G., Santana, I., Mönkäre, S., Kuuluvainen, L., Schleutker, J., Pöyhönen, M., Myllykangas, L., Senatore, A., Berchtold, D., Winek, K., Meisel, A., Pavlović, A., Kostić, V., Dobricic, V., Lohmann, E., Hanagasi, H., Guven, G., Bilgic, B., Bras, J., Guerreiro, R., Beule, D., Dirnagl, U.,& Sassi, C.. (2021). PHACTR1 genetic variability is not critical in small vessel ischemic disease patients and PcomA recruitment in C57BL/6J mice. in Scientific Reports
Nature Research., 11(1), 6072.
https://doi.org/10.1038/s41598-021-84919-x

Messerschmidt C, Foddis M, Blumenau S, Müller S, Bentele K, Holtgrewe M, Kun-Rodrigues C, Alonso I, do Carmo Macario M, Morgadinho AS, Velon AG, Santo G, Santana I, Mönkäre S, Kuuluvainen L, Schleutker J, Pöyhönen M, Myllykangas L, Senatore A, Berchtold D, Winek K, Meisel A, Pavlović A, Kostić V, Dobricic V, Lohmann E, Hanagasi H, Guven G, Bilgic B, Bras J, Guerreiro R, Beule D, Dirnagl U, Sassi C. PHACTR1 genetic variability is not critical in small vessel ischemic disease patients and PcomA recruitment in C57BL/6J mice. in Scientific Reports. 2021;11(1):6072.
doi:10.1038/s41598-021-84919-x .

Messerschmidt, Clemens, Foddis, Marco, Blumenau, Sonja, Müller, Susanne, Bentele, Kajetan, Holtgrewe, Manuel, Kun-Rodrigues, Celia, Alonso, Isabel, do Carmo Macario, Maria, Morgadinho, Ana Sofia, Velon, Ana Graça, Santo, Gustavo, Santana, Isabel, Mönkäre, Saana, Kuuluvainen, Liina, Schleutker, Johanna, Pöyhönen, Minna, Myllykangas, Liisa, Senatore, Assunta, Berchtold, Daniel, Winek, Katarzyna, Meisel, Andreas, Pavlović, Aleksandra, Kostić, Vladimir, Dobricic, Valerija, Lohmann, Ebba, Hanagasi, Hasmet, Guven, Gamze, Bilgic, Basar, Bras, Jose, Guerreiro, Rita, Beule, Dieter, Dirnagl, Ulrich, Sassi, Celeste, "PHACTR1 genetic variability is not critical in small vessel ischemic disease patients and PcomA recruitment in C57BL/6J mice" in Scientific Reports, 11, no. 1 (2021):6072,
https://doi.org/10.1038/s41598-021-84919-x . .