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1دورية أكاديمية
المؤلفون: Wilke, Martina, Haug, Heike, Funke, Joachim
المصدر: Wilke, Martina and Haug, Heike and Funke, Joachim (2008) Risk-specific search for risk-defusing operators. [Journal (Paginated)]
مصطلحات موضوعية: Psychology: Cognitive Psychology, Cognitive Psychology
الوصف: According to the concept of “active risk-defusing behavior”, decision makers in risky situations look for additional actions that reduce risk and allow them to favor the more risky alternative. Our study demonstrates that risk-defusing behavior depends on the type of risk (normal, medium, catastrophic or global) as well as on the domain (health, economy or ecology). In total, 12 scenarios (four risk types from three risk domains each) were constructed. Using the interview techniques of active information search and thinking-aloud, 120 interviews about decision-making processes with these scenarios were conducted. They showed that the active search for different risk-defusing operators depends on the type of risk, but even more on the domain of the scenario. Results suggest a need for further research about a typology of risk situations in which, besides formal classification criteria, content issues are also explored.
وصف الملف: application/pdf
الوصول الحر: http://cogprints.org/6628Test/
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2دورية أكاديمية
المؤلفون: Liepina, Lelde, Smith, Desiree E. C., Huidekoper, Hidde, Zeidler, Shimriet, Wamelink, Mirjam, de Wit, Marie-Claire, Wilke, Martina, Ruijter, George, Bierau, J. rgen, Blom, Henk J.
المصدر: Liepina , L , Smith , D E C , Huidekoper , H , Zeidler , S , Wamelink , M , de Wit , M-C , Wilke , M , Ruijter , G , Bierau , J R & Blom , H J 2024 , ' 5,10-methenyltetrahydrofolate synthetase deficiency : An extreme rare defect of folate metabolism in two Dutch siblings ' , JIMD Reports , vol. 65 , no. 2 , pp. 49-55 . https://doi.org/10.1002/jmd2.12409Test
الوصف: Two siblings, presenting with a neurometabolic phenotype, were identified with 5, 10-methenyltetrahydrofolate synthetase (MTHFS) deficiency. Whole genome sequencing in both patients demonstrated an homozygous MTHFS variant NM_006441.3(MTHFS):c.434G > A, p.Arg145Gin, which has been described before. At baseline, both patients showed moderate hyperhomocysteinemia, decreased 5-methyltetrahydrofolate (5MTHF), and increased 5-formyltetrahydrofolate (5-FTHF) in whole blood. In CSF, 5MTHF levels were in the low-normal range and 5-FTHF was strongly increased. In our novel enzyme assay, MTHFS activity was deficient in cultured fibroblasts in both sisters. Oral treatment was initiated with escalating dose of 5-methyltetrahydrofolate (5MTHF) up to 12 mg and hydroxycobalamin 5 mg daily. Plasma homocysteine normalized and 5MTHF became elevated in the blood of both patients. The elevated 5FTHF levels increased further on treatment in blood and CSF. This regimen resulted in some clinical improvement of patient 1. In patient 2, the clinical benefits of 5MTHF supplementation were less obvious. It seems plausible that the alleviation of the deficient 5MTHF levels and normalization of homocysteine in blood are of some clinical benefit. On the other hand, the very high levels of 5FTHF may well be detrimental and may prompt us to decrease the dose of 5MTHF. In addition, we hypothesize that the crippled MTHFS enzyme may destabilize the purinosome, which is presumably not ameliorated by 5MTHF.
الإتاحة: https://doi.org/10.1002/jmd2.12409Test
https://research.vumc.nl/en/publications/6e05f926-f728-4feb-8ec2-1043c9856a1cTest
http://www.scopus.com/inward/record.url?scp=85187638328&partnerID=8YFLogxKTest -
3دورية أكاديمية
المؤلفون: Albuainain, Fatimah, Shi, Yuwei, Lor-Zade, Sarah, Hüffmeier, Ulrike, Pauly, Melissa, Reis, André, Faivre, Laurence, Maraval, Julien, Bruel, Ange Line, Them, Frédéric Tran Mau, Haack, Tobias B., Grasshoff, Ute, Horber, Veronka, Schot, Rachel, van Slegtenhorst, Marjon, Wilke, Martina, Barakat, Tahsin Stefan
المصدر: Albuainain , F , Shi , Y , Lor-Zade , S , Hüffmeier , U , Pauly , M , Reis , A , Faivre , L , Maraval , J , Bruel , A L , Them , F T M , Haack , T B , Grasshoff , U , Horber , V , Schot , R , van Slegtenhorst , M , Wilke , M & Barakat , T S 2024 , ' Confirmation and expansion of the phenotype of the TCEAL1-related neurodevelopmental disorder ' , European Journal of Human Genetics , vol. 32 , no. ....
مصطلحات موضوعية: /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, name=SDG 3 - Good Health and Well-being
الوصف: Numerous contiguous gene deletion syndromes causing neurodevelopmental disorders have previously been defined using cytogenetics for which only in the current genomic era the disease-causing genes have become elucidated. One such example is deletion at Xq22.2, previously associated with a neurodevelopmental disorder which has more recently been found to be caused by de novo loss-of-function variants in TCEAL1. So far, a single study reported six unrelated individuals with this monogenetic disorder, presenting with syndromic features including developmental delay especially affecting expressive speech, intellectual disability, autistic-like behaviors, hypotonia, gait abnormalities and mild facial dysmorphism, in addition to ocular, gastrointestinal, and immunologic abnormalities. Here we report on four previously undescribed individuals, including two adults, with de novo truncating variants in TCEAL1, identified through trio exome or genome sequencing, further delineating the phenotype of the TCEAL1-related disorder. Whereas overall we identify similar features compared to the original report, we also highlight features in our adult individuals including hyperphagia, obesity, and endocrine abnormalities including hyperinsulinemia, hyperandrogenemia, and polycystic ovarian syndrome. X chromosome inactivation and RNA-seq studies further provide functional insights in the molecular mechanisms. Together this report expands the phenotypic and molecular spectrum of the TCEAL1-related disorder which will be useful for counseling of newly identified individuals and their families.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1038/s41431-023-01530-6Test
https://pure.eur.nl/en/publications/a93a40be-d95d-4721-87f8-429b9c1a21a3Test
https://pure.eur.nl/ws/files/125601358/Confirmation_and_expansion_of_the_phenotype_of_the_TCEAL1-related_neurodevelopmental_disorder.pdfTest
http://www.scopus.com/inward/record.url?scp=85181897717&partnerID=8YFLogxKTest -
4دورية أكاديمية
المؤلفون: Diderich, Karin E.M., Klapwijk, Jasmijn E., van der Schoot, Vyne, van den Born, Myrthe, Wilke, Martina, Joosten, Marieke, Stuurman, Kyra E., Hoefsloot, Lies H., Van Opstal, Diane, Brüggenwirth, Hennie T., Srebniak, Malgorzata I.
المصدر: Diderich , K E M , Klapwijk , J E , van der Schoot , V , van den Born , M , Wilke , M , Joosten , M , Stuurman , K E , Hoefsloot , L H , Van Opstal , D , Brüggenwirth , H T & Srebniak , M I 2024 , ' Response to the comment on Diderich et al. “The role of a multidisciplinary team in managing variants of uncertain clinical significance in prenatal genetic diagnosis” (EJMG 66(10),104844) ' , European Journal of Medical Genetics , vol. 67 , 104884 . https://doi.org/10.1016/j.ejmg.2023.104884Test
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1016/j.ejmg.2023.104884Test
https://pure.eur.nl/en/publications/9971203e-3eae-458d-a93d-21c5c5978975Test
https://pure.eur.nl/ws/files/120241866/Response_to_the_comment_on_Diderich_et_al._The_role_of_a_multidisciplinary_team_in_managing_variants_of_uncertain_clinical_significance_in_prenatal_genetic_diagnosis_EJMG_66_10_104844_.pdfTest
http://www.scopus.com/inward/record.url?scp=85177065122&partnerID=8YFLogxKTest -
5دورية أكاديمية
المؤلفون: Smith, Richard S, Kenny, Connor J, Ganesh, Vijay, Jang, Ahram, Borges-Monroy, Rebeca, Partlow, Jennifer N, Hill, R Sean, Shin, Taehwan, Chen, Allen Y, Doan, Ryan N, Anttonen, Anna-Kaisa, Ignatius, Jaakko, Medne, Livija, Bönnemann, Carsten G, Hecht, Jonathan L, Salonen, Oili, Barkovich, A James, Poduri, Annapurna, Wilke, Martina, de Wit, Marie Claire Y, Mancini, Grazia MS, Sztriha, Laszlo, Im, Kiho, Amrom, Dina, Andermann, Eva, Paetau, Ritva, Lehesjoki, Anna-Elina, Walsh, Christopher A, Lehtinen, Maria K
المصدر: Neuron. 99(5)
مصطلحات موضوعية: Biomedical and Clinical Sciences, Neurosciences, Pediatric, Epilepsy, Perinatal Period - Conditions Originating in Perinatal Period, Neurodegenerative, Brain Disorders, Stem Cell Research, Aetiology, Underpinning research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Adolescent, Adult, Animals, Cell Movement, Cells, Cultured, Cerebral Cortex, Child, Child, Preschool, Female, Ferrets, HEK293 Cells, Humans, Infant, Language Development, Male, Megalencephaly, Middle Aged, NAV1.3 Voltage-Gated Sodium Channel, Pedigree, Polymicrogyria, Sodium Channels, Cortical Development, Na(V)1.1, Na(V)1.3, Oromotor, Outer Radial Glia, SCN1A, SCN3A, Speech, Voltage-Gated Sodium Channel, Psychology, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
الوصف: Channelopathies are disorders caused by abnormal ion channel function in differentiated excitable tissues. We discovered a unique neurodevelopmental channelopathy resulting from pathogenic variants in SCN3A, a gene encoding the voltage-gated sodium channel NaV1.3. Pathogenic NaV1.3 channels showed altered biophysical properties including increased persistent current. Remarkably, affected individuals showed disrupted folding (polymicrogyria) of the perisylvian cortex of the brain but did not typically exhibit epilepsy; they presented with prominent speech and oral motor dysfunction, implicating SCN3A in prenatal development of human cortical language areas. The development of this disorder parallels SCN3A expression, which we observed to be highest early in fetal cortical development in progenitor cells of the outer subventricular zone and cortical plate neurons and decreased postnatally, when SCN1A (NaV1.1) expression increased. Disrupted cerebral cortical folding and neuronal migration were recapitulated in ferrets expressing the mutant channel, underscoring the unexpected role of SCN3A in progenitor cells and migrating neurons.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/1tg2r2ggTest
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6دورية أكاديمية
المؤلفون: Fasham, James, Huebner, Antje K., Liebmann, Lutz, Khalaf-Nazzal, Reham, Maroofian, Reza, Kryeziu, Nderim, Wortmann, Saskia B., Leslie, Joseph S., Ubeyratna, Nishanka, Mancini, Grazia M.S., van Slegtenhorst, Marjon, Wilke, Martina, Haack, Tobias B., Shamseldin, Hanan E., Gleeson, Joseph G., Almuhaizea, Mohamed, Dweikat, Imad, Abu-Libdeh, Bassam, Daana, Muhannad, Zaki, Maha S., Wakeling, Matthew N., McGavin, Lucy, Turnpenny, Peter D., Alkuraya, Fowzan S., Houlden, Henry, Schlattmann, Peter, Kaila, Kai, Crosby, Andrew H., Baple, Emma L., Hübner, Christian A.
المصدر: Fasham , J , Huebner , A K , Liebmann , L , Khalaf-Nazzal , R , Maroofian , R , Kryeziu , N , Wortmann , S B , Leslie , J S , Ubeyratna , N , Mancini , G M S , van Slegtenhorst , M , Wilke , M , Haack , T B , Shamseldin , H E , Gleeson , J G , Almuhaizea , M , Dweikat , I , Abu-Libdeh , B , Daana , M , Zaki , M S , Wakeling , M N , McGavin , L , ....
الوصف: SLC4A10 is a plasma-membrane bound transporter that utilizes the Na+ gradient to drive cellular HCO3- uptake, thus mediating acid extrusion. In the mammalian brain, SLC4A10 is expressed in principal neurons and interneurons, as well as in epithelial cells of the choroid plexus, the organ regulating the production of CSF. Using next generation sequencing on samples from five unrelated families encompassing nine affected individuals, we show that biallelic SLC4A10 loss-of-function variants cause a clinically recognizable neurodevelopmental disorder in humans. The cardinal clinical features of the condition include hypotonia in infancy, delayed psychomotor development across all domains and intellectual impairment. Affected individuals commonly display traits associated with autistic spectrum disorder including anxiety, hyperactivity and stereotyped movements. In two cases isolated episodes of seizures were reported in the first few years of life, and a further affected child displayed bitemporal epileptogenic discharges on EEG without overt clinical seizures. While occipitofrontal circumference was reported to be normal at birth, progressive postnatal microcephaly evolved in 7 out of 10 affected individuals. Neuroradiological features included a relative preservation of brain volume compared to occipitofrontal circumference, characteristic narrow sometimes 'slit-like' lateral ventricles and corpus callosum abnormalities. Slc4a10 -/- mice, deficient for SLC4A10, also display small lateral brain ventricles and mild behavioural abnormalities including delayed habituation and alterations in the two-object novel object recognition task. Collapsed brain ventricles in both Slc4a10-/- mice and affected individuals suggest an important role of SLC4A10 in the production of the CSF. However, it is notable that despite diverse roles of the CSF in the developing and adult brain, the cortex of Slc4a10-/- mice appears grossly intact. Co-staining with synaptic markers revealed that in neurons, SLC4A10 localizes to inhibitory, but ...
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1093/brain/awad235Test
https://pure.eur.nl/en/publications/397e68a8-7ec4-4486-b3a2-2d121f649fceTest
https://pure.eur.nl/ws/files/119321795/awad235.pdfTest
http://www.scopus.com/inward/record.url?scp=85171576785&partnerID=8YFLogxKTest -
7دورية أكاديمية
المؤلفون: Sheppard, Sarah E., Bryant, Laura, Wickramasekara, Rochelle N., Vaccaro, Courtney, Robertson, Brynn, Hallgren, Jodi, Hulen, Jason, Watson, Cynthia J., Faundes, Victor, Duffourd, Yannis, Lee, Pearl, Celeste Simon, M., de la Cruz, Xavier, Padilla, Natália, Flores-Mendez, Marco, Akizu, Naiara, Smiler, Jacqueline, Da Silva, Renata Pellegrino, Li, Dong, March, Michael, Diaz-Rosado, Abdias, de Barcelos, Isabella Peixoto, Choa, Zhao Xiang, Lim, Chin Yan, Dubourg, Christèle, Journel, Hubert, Demurger, Florence, Mulhern, Maureen, Akman, Cigdem, Lippa, Natalie, Andrews, Marisa, Baldridge, Dustin, Constantino, John, van Haeringen, Arie, Snoeck-Streef, Irina, Chow, Penny, Hing, Anne, Graham, John M., Au, Margaret, Faivre, Laurence, Shen, Wei, Mao, Rong, Palumbos, Janice, Viskochil, David, Gahl, William, Tifft, Cynthia, Macnamara, Ellen, Hauser, Natalie, Miller, Rebecca, Maffeo, Jessica, Afenjar, Alexandra, Doummar, Diane, Keren, Boris, Arn, Pamela, Macklin-Mantia, Sarah, Meerschaut, Ilse, Callewaert, Bert, Reis, André, Zweier, Christiane, Brewer, Carole, Saggar, Anand, Smeland, Marie F., Kumar, Ajith, Elmslie, Frances, Deshpande, Charu, Nizon, Mathilde, Cogne, Benjamin, van Ierland, Yvette, Wilke, Martina, van Slegtenhorst, Marjon, Koudijs, Suzanne, Chen, Jin Yun, Dredge, David, Pier, Danielle, Wortmann, Saskia, Kamsteeg, Erik Jan, Koch, Johannes, Haynes, Devon, Pollack, Lynda, Titheradge, Hannah, Ranguin, Kara, Denommé-Pichon, Anne Sophie, Weber, Sacha, de la Fuente, Rubén Pérez, del Pozo, Jaime Sánchez, Rosales, Jose Miguel Lezana, Joset, Pascal, Steindl, Katharina, Rauch, Anita, Mei, Davide, Mari, Francesco, Guerrini, Renzo, Lespinasse, James, Mau-Them, Frédéric Tran, Philippe, Christophe, Dauriat, Benjamin, Raymond, Laure, Moutton, Sébastien, Cueto-González, Anna M., Tan, Tiong Yang, Mignot, Cyril, Grotto, Sarah, Renaldo, Florence, Drivas, Theodore G., Hennessy, Laura, Raper, Anna, Parenti, Ilaria, Kaiser, Frank J., Kuechler, Alma, Busk, Øyvind L., Islam, Lily, Siedlik, Jacob A., Henderson, Lindsay B., Juusola, Jane, Person, Richard, Schnur, Rhonda E., Vitobello, Antonio, Banka, Siddharth, Bhoj, Elizabeth J., Stessman, Holly A.F.
المصدر: Sheppard , S E , Bryant , L , Wickramasekara , R N , Vaccaro , C , Robertson , B , Hallgren , J , Hulen , J , Watson , C J , Faundes , V , Duffourd , Y , Lee , P , Celeste Simon , M , de la Cruz , X , Padilla , N , Flores-Mendez , M , Akizu , N , Smiler , J , Da Silva , R P , Li , D , March , M , Diaz-Rosado , A , de Barcelos , I P , Choa ....
الوصف: Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5Brelated neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1126/sciadv.ade1463Test
https://pure.eur.nl/en/publications/6d222e2f-b72e-4d41-98ba-7a6d43099fa4Test
https://pure.eur.nl/ws/files/87092930/Mechanism_of_KMT5B_haploinsufficiency_in_neurodevelopment_in_humans_and_mice.pdfTest
http://www.scopus.com/inward/record.url?scp=85150009253&partnerID=8YFLogxKTest -
8دورية أكاديمية
المؤلفون: Niggl, Eva, Bouman, Arjan, Briere, Lauren C, Hoogenboezem, Remco M, Wallaard, Ilse, Park, Joohyun, Admard, Jakob, Wilke, Martina, Harris-Mostert, Emilio D R O, Elgersma, Minetta, Balasubramanian, Meena, Banka, Siddharth, Benke, Paul J, Bertrand, Miriam, Blesson, Alyssa E, Clayton-Smith, Jill, Ellingford, Jamie M, Gillentine, Madelyn A, Goodloe, Dana H, Haack, Tobias B, Jain, Mahim, Krantz, Ian, Luu, Sharon M, McPheron, Molly, Muss, Candace L, Raible, Sarah E, Robin, Nathaniel H, Sweetser, David A, Thiffault, Isabelle, Vetrini, Francesco, Witt, Dennis, Woods, Emily, Zhou, Dihong, Elgersma, Ype, van Esbroeck, Annelot C M
المصدر: Genomics England Research Consortium , Undiagnosed Diseases Network , Niggl , E , Bouman , A , Briere , L C , Hoogenboezem , R M , Wallaard , I , Park , J , Admard , J , Wilke , M , Harris-Mostert , E D R O , Elgersma , M , Balasubramanian , M , Banka , S , Benke , P J , Bertrand , M , Blesson , A E , Clayton-Smith , J , Ellingford , J M , Gillentine , M A , Goodloe , D H , Haack , T B ....
مصطلحات موضوعية: Humans, Intellectual Disability/genetics, Alternative Splicing/genetics, Heterogeneous-Nuclear Ribonucleoprotein Group C/genetics, Haploinsufficiency/genetics, Neurodevelopmental Disorders/genetics, Heterogeneous-Nuclear Ribonucleoproteins/genetics
الوصف: Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an essential, ubiquitously abundant protein involved in mRNA processing. Genetic variants in other members of the HNRNP family have been associated with neurodevelopmental disorders. Here, we describe 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five of them bear an identical in-frame deletion of nine amino acids in the extreme C terminus. To study the effect of this recurrent variant as well as HNRNPC haploinsufficiency, we used induced pluripotent stem cells (iPSCs) and fibroblasts obtained from affected individuals. While protein localization and oligomerization were unaffected by the recurrent C-terminal deletion variant, total HNRNPC levels were decreased. Previously, reduced HNRNPC levels have been associated with changes in alternative splicing. Therefore, we performed a meta-analysis on published RNA-seq datasets of three different cell lines to identify a ubiquitous HNRNPC-dependent signature of alternative spliced exons. The identified signature was not only confirmed in fibroblasts obtained from an affected individual but also showed a significant enrichment for genes associated with intellectual disability. Hence, we assessed the effect of decreased and increased levels of HNRNPC on neuronal arborization and neuronal migration and found that either condition affects neuronal function. Taken together, our data indicate that HNRNPC haploinsufficiency affects alternative splicing of multiple intellectual disability-associated genes and that the developing brain is sensitive to aberrant levels of HNRNPC. Hence, our data strongly support the inclusion of HNRNPC to the family of HNRNP-related neurodevelopmental disorders.
الإتاحة: https://doi.org/10.1016/j.ajhg.2023.07.005Test
https://research.manchester.ac.uk/en/publications/20dfa96c-7935-4341-8245-a4003ce04e04Test
http://www.scopus.com/inward/record.url?scp=85166598997&partnerID=8YFLogxKTest
https://www.mendeley.com/catalogue/b68f3a81-7e4e-3069-afa6-1e772c118567Test/ -
9دورية أكاديمية
مصطلحات موضوعية: AZF, Y chromosome microdeletion, Azoospermia, Gr/gr deletion, Human genetics, Male infertility, Oligozoospermia, Quality control, Spermatogenesis
الوصف: © 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. ; Testing for AZoospermia Factor (AZF) deletions of the Y chromosome is a key component of the diagnostic workup of azoospermic and severely oligozoospermic men. This revision of the 2013 European Academy of Andrology (EAA) and EMQN CIC (previously known as the European Molecular Genetics Quality Network) laboratory guidelines summarizes recent clinically relevant advances and provides an update on the results of the external quality assessment program jointly offered by both organizations. A basic multiplex PCR reaction followed by a deletion extension analysis remains the gold-standard methodology to detect and correctly interpret AZF deletions. Recent data have led to an update of the sY84 primer sequences, as well as to a refinement of what were previously considered as interchangeable border markers for AZFa and AZFb deletion breakpoints. More specifically, sY83 and sY143 are no longer recommended for the deletion extension analysis, leaving sY1064 and sY1192, respectively, as first-choice markers. Despite the transition, currently underway in several countries, toward a diagnosis based on certified kits, it should be noted that many of these commercial products are not recommended due to an unnecessarily high number of tested markers, and none of those currently available are, to the best of our knowledge, in accordance with the new first-choice markers for the deletion extension analysis. The gr/gr partial AZFc deletion remains a population-specific risk factor for impaired sperm production and a predisposing factor for testicular germ cell tumors. Testing for this deletion type is, as ...
العلاقة: info:eu-repo/grantAgreement/FCT/3599-PPCDT/EXPL%2FMEC-AND%2F0676%2F2021/PT; https://onlinelibrary.wiley.com/journal/20472927Test; Andrology. 2023 Sep 6; http://hdl.handle.net/10451/59357Test
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10دورية أكاديمية
المؤلفون: Brock, Stefanie, Laquerriere, Annie, Marguet, Florent, Myers, Scott J., Hongjie, Yuan, Baralle, Diana, Vanderhasselt, Tim, Stouffs, Katrien, Keymolen, Kathelijn, Kim, Sukhan, Allen, James, Shaulsky, Gil, Chelly, Jamel, Marcorelle, Pascale, Aziza, Jacqueline, Villard, Laurent, Sacaze, Elise, de Wit, Marie C. Y., Wilke, Martina, Mancini, Grazia Maria Simonetta, Hehr, Ute, Lim, Derek, Mansour, Sahar, Traynelis, Stephen F., Beneteau, Claire, Denis-Musquer, Marie, Jansen, Anna C., Fry, Andrew E., Bahi-Buisson, Nadia
الوصف: Background Malformations of cortical development (MCDs) have been reported in a subset of patients with pathogenic heterozygous variants in GRIN1 or GRIN2B, genes which encode for subunits of the N-methyl-D-aspartate receptor (NMDAR). The aim of this study was to further define the phenotypic spectrum of NMDAR-related MCDs. Methods We report the clinical, radiological and molecular features of 7 new patients and review data on 18 previously reported individuals with NMDAR-related MCDs. Neuropathological findings for two individuals with heterozygous variants in GRIN1 are presented. We report the clinical and neuropathological features of one additional individual with homozygous pathogenic variants in GRIN1. Results Heterozygous variants in GRIN1 and GRIN2B were associated with overlapping severe clinical and imaging features, including global developmental delay, epilepsy, diffuse dysgyria, dysmorphic basal ganglia and hippocampi. Neuropathological examination in two fetuses with heterozygous GRIN1 variants suggests that proliferation as well as radial and tangential neuronal migration are impaired. In addition, we show that neuronal migration is also impaired by homozygous GRIN1 variants in an individual with microcephaly with simplified gyral pattern. Conclusion These findings expand our understanding of the clinical and imaging features of the ‘NMDARopathy’ spectrum and contribute to our understanding of the likely underlying pathogenic mechanisms leading to MCD in these patients. Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Anonymised data from this study will be shared by request from any qualified investigator.
وصف الملف: application/pdf
العلاقة: https://orca.cardiff.ac.uk/id/eprint/149235/1/Brock_GRIN_manuscript_revision1_merged.pdfTest; Brock, Stefanie, Laquerriere, Annie, Marguet, Florent, Myers, Scott J., Hongjie, Yuan, Baralle, Diana, Vanderhasselt, Tim, Stouffs, Katrien, Keymolen, Kathelijn, Kim, Sukhan, Allen, James, Shaulsky, Gil, Chelly, Jamel, Marcorelle, Pascale, Aziza, Jacqueline, Villard, Laurent, Sacaze, Elise, de Wit, Marie C. Y., Wilke, Martina, Mancini, Grazia Maria Simonetta, Hehr, Ute, Lim, Derek, Mansour, Sahar, Traynelis, Stephen F., Beneteau, Claire, Denis-Musquer, Marie, Jansen, Anna C., Fry, Andrew E. https://orca.cardiff.ac.uk/view/cardiffauthors/A126971M.htmlTest orcid:0000-0001-9778-6924 orcid:0000-0001-9778-6924 and Bahi-Buisson, Nadia 2023. Overlapping cortical malformations in patients with pathogenic variants in GRIN1 and GRIN2B. Journal of Medical Genetics 60 (2) , pp. 183-192. 10.1136/jmedgenet-2021-107971 https://doi.org/10.1136/jmedgenet-2021-107971Test file https://orca.cardiff.ac.uk/id/eprint/149235/1/Brock_GRIN_manuscript_revision1_merged.pdfTest
الإتاحة: https://doi.org/10.1136/jmedgenet-2021-107971Test
https://orca.cardiff.ac.uk/id/eprint/149235Test/
https://orca.cardiff.ac.uk/id/eprint/149235/1/Brock_GRIN_manuscript_revision1_merged.pdfTest
