Search

Your search keyword '"Lyons, Greta"' showing total 132 results
Start Over Author "Lyons, Greta"
132 results on '"Lyons, Greta"'

2. Selenoprotein deficiency disorder predisposes to aortic aneurysm formation.

Author

Schoenmakers, Erik, Marelli, Federica, Jørgensen, Helle, Visser, W, Moran, Carla, Groeneweg, Stefan, Avalos, Carolina, Jurgens, Sean, Figg, Nichola, Finigan, Alison, Wali, Neha, Agostini, Maura, Wardle-Jones, Hannah, Lyons, Greta, Rusk, Rosemary, Gopalan, Deepa, Twiss, Philip, Visser, Jacob, Goddard, Martin, Nashef, Samer, Heijmen, Robin, Clift, Paul, Sinha, Sanjay, Pirruccello, James, Ellinor, Patrick, Busch-Nentwich, Elisabeth, Ramirez-Solis, Ramiro, Murphy, Michael, Persani, Luca, Bennett, Martin, and Chatterjee, Krishna

Subjects
Humans, Male, Mice, Animals, Zebrafish, Selenocysteine, Muscle, Smooth, Vascular, Aortic Aneurysm, Selenoproteins, Myocytes, Smooth Muscle
Abstract

Aortic aneurysms, which may dissect or rupture acutely and be lethal, can be a part of multisystem disorders that have a heritable basis. We report four patients with deficiency of selenocysteine-containing proteins due to selenocysteine Insertion Sequence Binding Protein 2 (SECISBP2) mutations who show early-onset, progressive, aneurysmal dilatation of the ascending aorta due to cystic medial necrosis. Zebrafish and male mice with global or vascular smooth muscle cell (VSMC)-targeted disruption of Secisbp2 respectively show similar aortopathy. Aortas from patients and animal models exhibit raised cellular reactive oxygen species, oxidative DNA damage and VSMC apoptosis. Antioxidant exposure or chelation of iron prevents oxidative damage in patients cells and aortopathy in the zebrafish model. Our observations suggest a key role for oxidative stress and cell death, including via ferroptosis, in mediating aortic degeneration.

Published
2023

5. Homozygous Resistance to Thyroid Hormone β: Can combined anti-thyroid drug and triiodothyroacetic acid treatment prevent cardiac failure?

Author

Moran, Carla, Habeb, Abdelhadi M, Kahaly, George J, Kampmann, Christoph, Hughes, Marina, Marek, Jan, Rajanayagam, Odelia, Kuczynski, Adam, Vargha-Khadem, Faraneh, Morsy, Mofeed, Offiah, Amaka C, Poole, Ken, Ward, Kate, Lyons, Greta, Halsall, David, Berman, Lol, Watson, Laura, Baguley, David, Mollon, John, Moore, Anthony T, Holder, Graham E, Dattani, Mehul, and Chatterjee, Krishna

Subjects
Clinical Research, Heart Disease, Cardiovascular, Aetiology, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, 2.1 Biological and endogenous factors, cardiac thyrotoxicosis, homozygous THRB mutation, resistance to thyroid hormone
Abstract

Resistance to thyroid hormone β (RTHβ) due to homozygous THRB defects is exceptionally rare, with only five kindreds reported worldwide. Cardiac dysfunction, which can be life-threatening, is recognized in the disorder. Here we describe the clinical, metabolic, ophthalmic, and cardiac findings in a 9-year-old boy harboring a biallelic THRB mutation (R243Q), along with biochemical, physiologic, and cardiac responses to carbimazole and triiodothyroacetic acid (TRIAC) therapy. The patient exhibits recognized features (goiter, nonsuppressed thyroid-stimulating hormone levels, upper respiratory tract infections, hyperactivity, low body mass index) of heterozygous RTHβ, with additional characteristics (dysmorphic facies, winging of scapulae) and more markedly elevated thyroid hormone levels, associated with the homozygous form of the disorder. Notably, an older sibling with similar clinical features and probable homozygous RTHβ had died of cardiac failure at age 13 years. Features of early dilated cardiomyopathy in our patient prompted combination treatment with carbimazole and TRIAC. Careful titration of therapy limited elevation in TSH levels and associated increase in thyroid volume. Subsequently, sustained reduction in thyroid hormones with normal TSH levels was reflected in lower basal metabolic rate, gain of lean body mass, and improved growth and cardiac function. A combination of antithyroid drug and TRIAC therapy may prevent thyrotoxic cardiomyopathy and its decompensation in homozygous or even heterozygous RTHβ in which life-threatening hyperthyroid features predominate.

Published
2017

6. Homozygous Resistance to Thyroid Hormone β: Can Combined Antithyroid Drug and Triiodothyroacetic Acid Treatment Prevent Cardiac Failure?

Author

Moran, Carla, Habeb, Abdelhadi M, Kahaly, George J, Kampmann, Christoph, Hughes, Marina, Marek, Jan, Rajanayagam, Odelia, Kuczynski, Adam, Vargha-Khadem, Faraneh, Morsy, Mofeed, Offiah, Amaka C, Poole, Ken, Ward, Kate, Lyons, Greta, Halsall, David, Berman, Lol, Watson, Laura, Baguley, David, Mollon, John, Moore, Anthony T, Holder, Graham E, Dattani, Mehul, and Chatterjee, Krishna

Subjects
cardiac thyrotoxicosis, homozygous THRB mutation, resistance to thyroid hormone
Abstract

Resistance to thyroid hormone β (RTHβ) due to homozygous THRB defects is exceptionally rare, with only five kindreds reported worldwide. Cardiac dysfunction, which can be life-threatening, is recognized in the disorder. Here we describe the clinical, metabolic, ophthalmic, and cardiac findings in a 9-year-old boy harboring a biallelic THRB mutation (R243Q), along with biochemical, physiologic, and cardiac responses to carbimazole and triiodothyroacetic acid (TRIAC) therapy. The patient exhibits recognized features (goiter, nonsuppressed thyroid-stimulating hormone levels, upper respiratory tract infections, hyperactivity, low body mass index) of heterozygous RTHβ, with additional characteristics (dysmorphic facies, winging of scapulae) and more markedly elevated thyroid hormone levels, associated with the homozygous form of the disorder. Notably, an older sibling with similar clinical features and probable homozygous RTHβ had died of cardiac failure at age 13 years. Features of early dilated cardiomyopathy in our patient prompted combination treatment with carbimazole and TRIAC. Careful titration of therapy limited elevation in TSH levels and associated increase in thyroid volume. Subsequently, sustained reduction in thyroid hormones with normal TSH levels was reflected in lower basal metabolic rate, gain of lean body mass, and improved growth and cardiac function. A combination of antithyroid drug and TRIAC therapy may prevent thyrotoxic cardiomyopathy and its decompensation in homozygous or even heterozygous RTHβ in which life-threatening hyperthyroid features predominate.

Published
2017

7. Disease characteristics of MCT8 deficiency: an international, retrospective, multicentre cohort study

Author

Groeneweg, Stefan, van Geest, Ferdy S, Abacı, Ayhan, Alcantud, Alberto, Ambegaonkar, Gautam P, Armour, Christine M, Bakhtiani, Priyanka, Barca, Diana, Bertini, Enrico S, van Beynum, Ingrid M, Brunetti-Pierri, Nicola, Bugiani, Marianna, Cappa, Marco, Cappuccio, Gerarda, Castellotti, Barbara, Castiglioni, Claudia, Chatterjee, Krishna, de Coo, Irenaeus F M, Coutant, Régis, Craiu, Dana, Crock, Patricia, DeGoede, Christian, Demir, Korcan, Dica, Alice, Dimitri, Paul, Dolcetta-Capuzzo, Anna, Dremmen, Marjolein H G, Dubey, Rachana, Enderli, Anina, Fairchild, Jan, Gallichan, Jonathan, George, Belinda, Gevers, Evelien F, Hackenberg, Annette, Halász, Zita, Heinrich, Bianka, Huynh, Tony, Kłosowska, Anna, van der Knaap, Marjo S, van der Knoop, Marieke M, Konrad, Daniel, Koolen, David A, Krude, Heiko, Lawson-Yuen, Amy, Lebl, Jan, Linder-Lucht, Michaela, Lorea, Cláudia F, Lourenço, Charles M, Lunsing, Roelineke J, Lyons, Greta, Malikova, Jana, Mancilla, Edna E, McGowan, Anne, Mericq, Veronica, Lora, Felipe M, Moran, Carla, Müller, Katalin E, Oliver-Petit, Isabelle, Paone, Laura, Paul, Praveen G, Polak, Michel, Porta, Francesco, Poswar, Fabiano O, Reinauer, Christina, Rozenkova, Klara, Menevse, Tuba S, Simm, Peter, Simon, Anna, Singh, Yogen, Spada, Marco, van der Spek, Jet, Stals, Milou A M, Stoupa, Athanasia, Subramanian, Gopinath M, Tonduti, Davide, Turan, Serap, den Uil, Corstiaan A, Vanderniet, Joel, van der Walt, Adri, Wémeau, Jean-Louis, Wierzba, Jolante, de Wit, Marie-Claire Y, Wolf, Nicole I, Wurm, Michael, Zibordi, Federica, Zung, Amnon, Zwaveling-Soonawala, Nitash, and Visser, W Edward

Published
2020
Full Text
View/download PDF

9. Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial

Author

Groeneweg, Stefan, Peeters, Robin P, Moran, Carla, Stoupa, Athanasia, Auriol, Françoise, Tonduti, Davide, Dica, Alice, Paone, Laura, Rozenkova, Klara, Malikova, Jana, van der Walt, Adri, de Coo, Irenaeus F M, McGowan, Anne, Lyons, Greta, Aarsen, Femke K, Barca, Diana, van Beynum, Ingrid M, van der Knoop, Marieke M, Jansen, Jurgen, Manshande, Martien, Lunsing, Roelineke J, Nowak, Stan, den Uil, Corstiaan A, Zillikens, M Carola, Visser, Frank E, Vrijmoeth, Paul, de Wit, Marie Claire Y, Wolf, Nicole I, Zandstra, Angelique, Ambegaonkar, Gautam, Singh, Yogen, de Rijke, Yolanda B, Medici, Marco, Bertini, Enrico S, Depoorter, Sylvia, Lebl, Jan, Cappa, Marco, De Meirleir, Linda, Krude, Heiko, Craiu, Dana, Zibordi, Federica, Oliver Petit, Isabelle, Polak, Michel, Chatterjee, Krishna, Visser, Theo J, and Visser, W Edward

Published
2019
Full Text
View/download PDF

10. Approach to the Patient With Raised Thyroid Hormones and Nonsuppressed TSH.

Author

Moran, Carla, Schoenmakers, Nadia, Halsall, David, Oddy, Susan, Lyons, Greta, van den Berg, Sjoerd, Gurnell, Mark, and Chatterjee, Krishna

Abstract

Measurement of free thyroid hormones (THs) and thyrotropin (TSH) using automated immunoassays is central to the diagnosis of thyroid dysfunction. Using illustrative cases, we describe a diagnostic approach to discordant thyroid function tests, focusing on entities causing elevated free thyroxine and/or free triiodothyronine measurements with nonsuppressed TSH levels. Different types of analytical interference (eg, abnormal thyroid hormone binding proteins, antibodies to iodothyronines or TSH, heterophile antibodies, biotin) or disorders (eg, resistance to thyroid hormone β or α, monocarboxylate transporter 8 or selenoprotein deficiency, TSH-secreting pituitary tumor) that can cause this biochemical pattern will be considered. We show that a structured approach, combining clinical assessment with additional laboratory investigations to exclude assay artifact, followed by genetic testing or specialized imaging, can establish a correct diagnosis, potentially preventing unnecessary investigation or inappropriate therapy. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

12. Resistance to thyroid hormone induced tachycardia in RTHα syndrome

Author

Dore, Riccardo, primary, Watson, Laura, additional, Hollidge, Stefanie, additional, Krause, Christin, additional, Sentis, Sarah Christine, additional, Oelkrug, Rebecca, additional, Geißler, Cathleen, additional, Johann, Kornelia, additional, Pedaran, Mehdi, additional, Lyons, Greta, additional, Lopez-Alcantara, Nuria, additional, Resch, Julia, additional, Sayk, Friedhelm, additional, Iwen, Karl Alexander, additional, Franke, Andre, additional, Boysen, Teide Jens, additional, Dalley, Jeffrey W., additional, Lorenz, Kristina, additional, Moran, Carla, additional, Rennie, Kirsten L., additional, Arner, Anders, additional, Kirchner, Henriette, additional, Chatterjee, Krishna, additional, and Mittag, Jens, additional

Published
2023
Full Text
View/download PDF

13. Centile reference chart for resting metabolic rate through the life course

Author

Watson, Laura, Cole, Tim J, Lyons, Greta, Georgiou, Christopher, Worsley, Jieniean, Carr, Katherine, Murgatroyd, Peter, Moran, Carla, Chatterjee, Krishna, Venables, Michelle, Watson, Laura [0000-0002-2120-3531], Cole, Tim J [0000-0001-5711-8200], Chatterjee, Krishna [0000-0002-2654-8854], Venables, Michelle [0000-0002-9380-0060], and Apollo - University of Cambridge Repository

Subjects
Adult, Adolescent, Original research, growth, Body Weight, Middle Aged, adolescent health, Body Mass Index, paediatrics, Life Change Events, endocrinology, Young Adult, Absorptiometry, Photon, Pediatrics, Perinatology and Child Health, physiology, Body Composition, Humans, Basal Metabolism, Child, Energy Metabolism
Abstract

Peer reviewed: True, Acknowledgements: We would like to thank the participants and their families for taking part in our research., Funder: NIHR Cambridge Clinical Research Facility, Cambridge, UK, Objective: Reference centile charts are widely used for the assessment of growth and have progressed from describing height and weight to include body composition variables such as fat and lean mass. Here, we present centile charts for an index of resting energy expenditure (REE) or metabolic rate, adjusted for lean mass versus age, including both children and adults across the life course. Design, participants and intervention: Measurements of REE by indirect calorimetry and body composition using dual-energy X-ray absorptiometry were made in 411 healthy children and adults (age range 6–64 years) and serially in a patient with resistance to thyroid hormone α (RTHα) between age 15 and 21 years during thyroxine therapy. Setting: NIHR Cambridge Clinical Research Facility, UK. Results: The centile chart indicates substantial variability, with the REE index ranging between 0.41 and 0.59 units at age 6 years, and 0.28 and 0.40 units at age 25 years (2nd and 98th centile, respectively). The 50th centile of the index ranged from 0.49 units (age 6 years) to 0.34 units (age 25 years). Over 6 years, the REE index of the patient with RTHα varied from 0.35 units (25th centile) to 0.28 units (

Published
2023

14. Resistance to thyroid hormone induced tachycardia in RTHα syndrome

Author

Dore, Riccardo, Watson, Laura, Hollidge, Stefanie, Krause, Christin, Sentis, Sarah Christine, Oelkrug, Rebecca, Geißler, Cathleen, Johann, Kornelia, Pedaran, Mehdi, Lyons, Greta, Lopez-Alcantara, Nuria, Resch, Julia, Sayk, Friedhelm, Iwen, Karl Alexander, Franke, Andre, Boysen, Teide Jens, Dalley, Jeffrey W, Lorenz, Kristina, Moran, Carla, Rennie, Kirsten L, Arner, Anders, Kirchner, Henriette, Chatterjee, Krishna, Mittag, Jens, Dore, Riccardo [0000-0001-5988-9885], Johann, Kornelia [0000-0002-5089-7237], Franke, Andre [0000-0003-1530-5811], Dalley, Jeffrey W [0000-0002-2282-3660], Chatterjee, Krishna [0000-0002-2654-8854], Mittag, Jens [0000-0001-7778-5158], and Apollo - University of Cambridge Repository

Subjects
Thyroid Hormone Resistance Syndrome, Male, Mice, Thyroid Hormones, Thyroxine, Tachycardia, Mutation, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Animals, Thyroid Hormone Receptors alpha
Abstract

Mutations in thyroid hormone receptor α1 (TRα1) cause Resistance to Thyroid Hormone α (RTHα), a disorder characterized by hypothyroidism in TRα1-expressing tissues including the heart. Surprisingly, we report that treatment of RTHα patients with thyroxine to overcome tissue hormone resistance does not elevate their heart rate. Cardiac telemetry in male, TRα1 mutant, mice indicates that such persistent bradycardia is caused by an intrinsic cardiac defect and not due to altered autonomic control. Transcriptomic analyses show preserved, thyroid hormone (T3)-dependent upregulation of pacemaker channels (Hcn2, Hcn4), but irreversibly reduced expression of several ion channel genes controlling heart rate. Exposure of TRα1 mutant male mice to higher maternal T3 concentrations in utero, restores altered expression and DNA methylation of ion channels, including Ryr2. Our findings indicate that target genes other than Hcn2 and Hcn4 mediate T3-induced tachycardia and suggest that treatment of RTHα patients with thyroxine in high dosage without concomitant tachycardia, is possible.

Published
2023

17. The Impact of the COVID-19 Pandemic on Alcohol Consumption and Alcohol Problems: A Prospective Study in a Community Sample of Heavy Drinking Young Adults

Author

Creswell, Kasey, Wright, Aidan, Hisler, Garrett, Kumar, Lakshmi, and Lyons, Greta

Subjects
Social and Behavioral Sciences, Education
Abstract

The impact of the COVID-19 pandemic on alcohol consumption remains unclear. The vast majority of studies published on this topic have used cross-sectional designs that required participants to retrospectively recall changes in their alcohol consumption from pre- to post-pandemic, with inconsistent results. A handful of longitudinal studies have been published using college student samples and population-based surveys of adults, also with inconsistent results. This study will prospectively examine within-person changes in alcohol consumption and alcohol-related problems in heavy drinking young adults before and after the start of the COVID-19 pandemic. We will also test theoretically informed mechanisms (i.e., increases in negative affectivity and coping-motivated drinking) in explaining pandemic-related changes in alcohol consumption and alcohol problems. Given some data suggesting that women (vs. men) may be especially likely to increase their drinking as a result of the pandemic, we will test for gender differences in alcohol consumption from pre- to post-pandemic. Study Aims 1. Describe changes in drinking patterns as a result of the pandemic (e.g., shifts in whether drinking primarily occurs on weekends vs. weekdays and in social vs. solitary contexts). 2. Test whether women were particularly likely to increase their drinking as a result of the pandemic. 3. Test whether changes in drinking and alcohol problems are explained by changes in negative affectivity and coping-motivated drinking.

Published
2022
Full Text
View/download PDF

18. Resistance to thyroid hormone alpha: molecular, biochemical and physiological approach to diagnosis and therapy

Author

Agostini, Maura, primary, Pietzner, Maik, additional, Marelli, Federica, additional, Prapa, Matina, additional, Moran, Carla, additional, Edward, Visser W., additional, Brown, Dave, additional, Thomas, Ellen, additional, Schoenmakers, Erik, additional, Romartinez-Alonso, Beatriz, additional, Scheuplein, Rabea, additional, Tylki-Szymanska, Anna, additional, Lyons, Greta, additional, Watson, Laura, additional, Rajanayagam, Odelia, additional, Schwedhelm, Edzard, additional, F., Hartmann Michaela, additional, Wudy, Stefan, additional, Probst, Maiken, additional, MacDonald, Stephen, additional, Thomas, William, additional, Arlt, Wiebke, additional, Volker, Uwe, additional, M., Main Katharina, additional, Feldt-Rasmussen, Ulla, additional, T., Dattani Mehul, additional, Koren, Dahll Louise, additional, Demir, Korcan, additional, Kara, Cengiz, additional, Kirbiyik, Ozgur, additional, Mammadova, Jamala, additional, Cayır, Atilla, additional, Yarali, Oguzhan, additional, Phan-Hug, Franziska, additional, Sakremath, Rajesh, additional, Mohamed, Zainaba, additional, Shinawi, Marwan, additional, Gill, Harpreet, additional, pacaud, Daniele, additional, Perrier, Renee, additional, Poke, Gemma, additional, Hunter, Wendy, additional, Douzgou, Sofia, additional, Wakeling, Emma, additional, Gardham, Alice, additional, Lim, Derek, additional, Shears, Deborah, additional, Freel, Marie, additional, Omladic, Jasna, additional, Tansek, Mojca, additional, Writzl, Karin, additional, Farooqi, Sadaf, additional, Kopp, Peter, additional, Schwabe, John, additional, Persani, Luca, additional, and Chatterjee, Krishna, additional

Published
2022
Full Text
View/download PDF

19. Selenoprotein deficiency disorder predisposes to aortic aneurysm formation

Author

Schoenmakers, Erik, primary, Marelli, Federica, additional, Jorgensen, Helle, additional, Edward, Visser W., additional, Moran, Carla, additional, Groeneweg, Stefan, additional, Avalos, Carolina, additional, Figg, Nichola, additional, Finigan, Alison, additional, Wali, Neha, additional, Agostini, Maura, additional, Wardle-Jones, Hannah, additional, Lyons, Greta, additional, Rusk, Rosemary, additional, Gopalan, Deepa, additional, Johannes, Visser Jacob, additional, Goddard, Martin, additional, Nashef, Samer, additional, Heijmen, Robin, additional, Clift, Paul, additional, Sinha, Sanjay, additional, Busch-Nentwich, Elisabeth, additional, Ramirez-Solis, Ramiro, additional, Persani, Luca, additional, Bennett, Martin, additional, and Chatterjee, Krishna, additional

Published
2022
Full Text
View/download PDF

21. Resistance to thyroid hormone caused by a mutation in thyroid hormone receptor (TR)α1 and TRα2: clinical, biochemical, and genetic analyses of three related patients

Author

Moran, Carla, Agostini, Maura, Visser, W Edward, Schoenmakers, Erik, Schoenmakers, Nadia, Offiah, Amaka C, Poole, Ken, Rajanayagam, Odelia, Lyons, Greta, Halsall, David, Gurnell, Mark, Chrysis, Dionisios, Efthymiadou, Alexandra, Buchanan, Charles, Aylwin, Simon, and Chatterjee, Krishna K

Published
2014
Full Text
View/download PDF

22. Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis

Author

Schoenmakers, Erik, Carlson, Bradley, Agostini, Maura, Moran, Carla, Rajanayagam, Odelia, Bochukova, Elena, Tobe, Ryuta, Peat, Rachel, Gevers, Evelien, Muntoni, Francesco, Guicheney, Pascale, Schoenmakers, Nadia, Farooqi, Sadaf, Lyons, Greta, Hatfield, Dolph, and Chatterjee, Krishna

Subjects
Genomics -- Genetic aspects -- Research, Amino acids -- Research, Transfer RNA -- Research, Health care industry
Abstract

Selenium is a trace element that is essential for human health and is incorporated into more than 25 human selenocysteine-containing (Sec-containing) proteins via unique Sec-insertion machinery that includes a specific, nuclear genome-encoded, transfer RNA ([tRNA.sup.[Ser]Sec]). Here, we have identified a human [tRNA.sup.[Ser]Sec] mutation in a proband who presented with a variety of symptoms, including abdominal pain, fatigue, muscle weakness, and low plasma levels of selenium. This mutation resulted in a marked reduction in expression of stress-related, but not housekeeping, selenoproteins. Evaluation of primary cells from the homozygous proband and a heterozygous parent indicated that the observed deficit in stress- related selenoprotein production is likely mediated by reduced expression and diminished 2'-O-methylribosylation at uridine 34 in mutant [tRNA.sup.[Ser]Sec]. Moreover, this methylribosylation defect was restored by cellular complementation with normal [tRNA.sup.[Ser]Sec]. This study identifies a tRNA mutation that selectively impairs synthesis of stress-related selenoproteins and demonstrates the importance of tRNA modification for normal selenoprotein synthesis., Introduction The 21st proteinogenic amino acid, selenocysteine (Sec), is a constituent of more than 25 human selenoproteins. Sec incorporation requires UGA codons in selenoprotein mRNAs to be decoded as Sec, [...]

Published
2016
Full Text
View/download PDF

23. Indirect effects of personality on high‐intensity drinking: The role of drinking motives.

Author

Bachrach, Rachel L., Zhou, Agnes, Kumar, Lakshmi, Lyons, Greta, Skrzynski, Carillon J., and Creswell, Kasey G.

Subjects
BINGE drinking, RISK assessment, RESEARCH funding, PATH analysis (Statistics), DEATH, PSYCHOLOGICAL adaptation, LONGITUDINAL method
Abstract

Background: Researchers have long been interested in identifying risk factors for binge drinking behavior (4+/5+ drinks/occasion for females/males), but many studies have demonstrated that a substantial proportion of young adults are drinking at levels far beyond (often 2 to 3 times) the standard binge threshold. The consumption of such large quantities of alcohol, typically referred to as high‐intensity drinking (HID), can cause severe alcohol‐related problems, such as blackouts, unintended sexual experiences, and death. This study is the first to investigate whether personality is indirectly associated with the likelihood of HID via drinking motives in a large (N = 999) sample of underage young adult drinkers. We hypothesized that trait neuroticism would be indirectly associated with the likelihood of HID via coping motives and that extraversion would be indirectly associated with the likelihood of HID via social and enhancement motives. Methods: To investigate these hypotheses, we used two archival data sets that recruited current underage (18‐ to 20‐year‐old) adult drinkers residing in the United States from online panel services. Participants completed self‐report survey items assessing constructs of interest. To investigate the role of drinking motives in the association between personality and HID, both the direct and indirect effects were calculated via three path analyses. Results: Findings revealed that neuroticism was partially indirectly associated with the likelihood of HID via coping motives (b = 0.02, SE = 0.004, p < 0.01). In addition, extraversion was indirectly associated with the likelihood of HID via social (b = 0.031, SE = 0.002, p < 0.01) and enhancement motives (b = 0.01, SE = 0.002, p = 0.01). Conclusions: These findings are an initial step in examining the interplay among personality traits, drinking motives, and HID in underage drinkers and point to the need for longitudinal studies assessing these associations. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

24. Long-Term Efficacy of T3 Analogue Triac in Children and Adults With MCT8 Deficiency: A Real-Life Retrospective Cohort Study

Author

van Geest, Ferdy S, primary, Groeneweg, Stefan, additional, van den Akker, Erica L T, additional, Bacos, Iuliu, additional, Barca, Diana, additional, van den Berg, Sjoerd A A, additional, Bertini, Enrico, additional, Brunner, Doris, additional, Brunetti-Pierri, Nicola, additional, Cappa, Marco, additional, Cappuccio, Gerarda, additional, Chatterjee, Krishna, additional, Chesover, Alexander D, additional, Christian, Peter, additional, Coutant, Régis, additional, Craiu, Dana, additional, Crock, Patricia, additional, Dewey, Cheyenne, additional, Dica, Alice, additional, Dimitri, Paul, additional, Dubey, Rachana, additional, Enderli, Anina, additional, Fairchild, Jan, additional, Gallichan, Jonathan, additional, Garibaldi, Luigi R, additional, George, Belinda, additional, Hackenberg, Annette, additional, Heinrich, Bianka, additional, Huynh, Tony, additional, Kłosowska, Anna, additional, Lawson-Yuen, Amy, additional, Linder-Lucht, Michaela, additional, Lyons, Greta, additional, Monti Lora, Felipe, additional, Moran, Carla, additional, Müller, Katalin E, additional, Paone, Laura, additional, Paul, Praveen G, additional, Polak, Michel, additional, Porta, Francesco, additional, Reinauer, Christina, additional, de Rijke, Yolanda B, additional, Seckold, Rowen, additional, Menevşe, Tuba Seven, additional, Simm, Peter, additional, Simon, Anna, additional, Spada, Marco, additional, Stoupa, Athanasia, additional, Szeifert, Lilla, additional, Tonduti, Davide, additional, van Toor, Hans, additional, Turan, Serap, additional, Vanderniet, Joel, additional, de Waart, Monique, additional, van der Wal, Ronald, additional, van der Walt, Adri, additional, van Wermeskerken, Anne-Marie, additional, Wierzba, Jolanta, additional, Zibordi, Federica, additional, Zung, Amnon, additional, Peeters, Robin P, additional, and Visser, W Edward, additional

Published
2021
Full Text
View/download PDF

25. Germ Line Mutations in the Thyroid Hormone Receptor Alpha Gene Predispose to Cutaneous Tags and Melanocytic Nevi

Author

Di Cicco, Emery, primary, Moran, Carla, additional, Visser, W. Edward, additional, Nappi, Annarita, additional, Schoenmakers, Erik, additional, Todd, Pamela, additional, Lyons, Greta, additional, Dattani, Mehul, additional, Ambrosio, Raffaele, additional, Parisi, Silvia, additional, Salvatore, Domenico, additional, Chatterjee, Krishna, additional, and Dentice, Monica, additional

Published
2021
Full Text
View/download PDF

26. Challenges and opportunities for conducting a vaccine trial during the COVID-19 pandemic in the United Kingdom

Author

Török, M Estée, primary, Underwood, Benjamin R, additional, Toshner, Mark, additional, Waddington, Claire, additional, Sidhom, Emad, additional, Sharrocks, Katherine, additional, Bousfield, Rachel, additional, Summers, Charlotte, additional, Saunders, Caroline, additional, McIntyre, Zoe, additional, Morris, Helen, additional, Piper, Jo, additional, Calderon, Gloria, additional, Dennis, Sarah, additional, Assari, Tracy, additional, de Rotrou, Anita Marguerie, additional, Shaw, Ashley, additional, Bradley, John, additional, O’Brien, John, additional, Rintoul, Robert C, additional, Smith, Ian, additional, Bullmore, Ed, additional, Chatterjee, Krishna, additional, Ribeiro, Carla, additional, Pickup, Lorinda, additional, de Jesus, Ranalie, additional, Brookes, Karen, additional, Vargas, Phoebe, additional, McMahon, Caroline, additional, Macor, Chiara, additional, Pasquale, Ciro, additional, Bermperi, Areti, additional, Kourampa, Evgenia, additional, Fabiculcana, Marivic, additional, Zerudo, Julie Ann, additional, Mendoza, Vivien, additional, Fuller, Stewart, additional, Glemas, Claire, additional, Baker, Sharon, additional, Lyons, Greta, additional, Bishop, Marina, additional, Coleman, Siobhan, additional, Thomas, Naomi, additional, Mlilo, Vince, additional, Stanton, Edward, additional, Michel, Rachel, additional, Philips, Julie, additional, Rice, Heidi, additional, Garner, Lucie, additional, Rosa, Francesca, additional, Victor, Saji, additional, Zamikula, Julie, additional, Mepham, Sue, additional, Hajee, Fatima, additional, Quijano-Campos, Juan Carlos, additional, Watson, Laura, additional, Georgiou, Christopher, additional, Worsley, Jieniean, additional, Shamtally-Amode, Djamilla, additional, Rahimi, Ferishta, additional, Jones, Heather, additional, Cruz, Isabel, additional, Lindsay, Gayle, additional, Sparke, Christian, additional, Chapman, Anna, additional, Keating-Fedders, Katie, additional, Fahey, Codie, additional, Johnson, Danielle, additional, Worboys, Lucy, additional, Hargreaves, Simone, additional, Bucke, Ashlea, additional, Carr, Lindsay, additional, Hampshire, Jackie, additional, Richardson, Tracy, additional, Sharpe, Jenny, additional, Whitehead, Lynne, additional, Vyse, Naval, additional, Kelleher, Stephen, additional, Sherwood, Mary-Beth, additional, Hughes, Vicki, additional, and Giraud, Kim, additional

Published
2021
Full Text
View/download PDF

27. A Novel Albumin Gene Mutation (R222I) in Familial Dysalbuminemic Hyperthyroxinemia

Author

Schoenmakers, Nadia, Moran, Carla, Campi, Irene, Agostini, Maura, Bacon, Olivia, Rajanayagam, Odelia, Schwabe, John, Bradbury, Sonia, Barrett, Timothy, Geoghegan, Frank, Druce, Maralyn, Beck-Peccoz, Paolo, OʼToole, Angela, Clark, Penelope, Bignell, Michelle, Lyons, Greta, Halsall, David, Gurnell, Mark, and Chatterjee, Krishna

Published
2014

30. Hyperthyroxinemia and Hypercortisolemia due to Familial Dysalbuminemia

Author

Moran, Carla, primary, Seger, Christoph, additional, Taylor, Kevin, additional, Oddy, Susan, additional, Burling, Keith, additional, Rajanayagam, Odelia, additional, Fairall, Louise, additional, McGowan, Anne, additional, Lyons, Greta, additional, Halsall, David, additional, Gurnell, Mark, additional, Schwabe, John, additional, Chatterjee, Krishna, additional, and Strey, Christopher, additional

Published
2020
Full Text
View/download PDF

33. Long-Term Efficacy of T3 Analogue Triac in Children and Adults With MCT8 Deficiency: A Real-Life Retrospective Cohort Study

Author

van Geest, Ferdy S, Groeneweg, Stefan, van den Akker, Erica L T, Bacos, Iuliu, Barca, Diana, van den Berg, Sjoerd A A, Bertini, Enrico, Brunner, Doris, Brunetti-Pierri, Nicola, Cappa, Marco, Cappuccio, Gerarda, Chatterjee, Krishna, Chesover, Alexander D, Christian, Peter, Coutant, Régis, Craiu, Dana, Crock, Patricia, Dewey, Cheyenne, Dica, Alice, Dimitri, Paul, Dubey, Rachana, Enderli, Anina, Fairchild, Jan, Gallichan, Jonathan, Garibaldi, Luigi R, George, Belinda, Hackenberg, Annette, Heinrich, Bianka, Huynh, Tony, Kłosowska, Anna, Lawson-Yuen, Amy, Linder-Lucht, Michaela, Lyons, Greta, Monti Lora, Felipe, Moran, Carla, Müller, Katalin E, Paone, Laura, Paul, Praveen G, Polak, Michel, Porta, Francesco, Reinauer, Christina, de Rijke, Yolanda B, Seckold, Rowen, Menevşe, Tuba Seven, Simm, Peter, Simon, Anna, Spada, Marco, Stoupa, Athanasia, Szeifert, Lilla, Tonduti, Davide, van Toor, Hans, Turan, Serap, Vanderniet, Joel, de Waart, Monique, van der Wal, Ronald, van der Walt, Adri, van Wermeskerken, Anne-Marie, Wierzba, Jolanta, Zibordi, Federica, Zung, Amnon, Peeters, Robin P, and Visser, W Edward

Published
2022
Full Text
View/download PDF

34. A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome

Author

Roche, Edna F, McGowan, Anne, Koulouri, Olympia, Turgeon, Marc-Olivier, Nicholas, Adeline K, Heffernan, Emmeline, El-Khairi, Ranna, Abid, Noina, Lyons, Greta, Halsall, David, Bonomi, Marco, Persani, Luca, Dattani, Mehul T, Gurnell, Mark, Bernard, Daniel J, Schoenmakers, Nadia, Gurnell, Mark [0000-0001-5745-6832], Schoenmakers, Nadia [0000-0002-0847-2884], and Apollo - University of Cambridge Repository

Abstract

Objective Loss-of-function mutations in IGSF1 result in X-linked central congenital hypothyroidism (CeCH), occurring in isolation or associated with additional pituitary hormone deficits. Intrafamilial penetrance is highly variable and a minority of heterozygous females are also affected. We identified and characterized a novel IGSF1 mutation and investigated its associated phenotypes in a large Irish kindred. Design, Patients & Measurements A novel hemizygous IGSF1 mutation was identified by direct sequencing in two brothers with CeCH and its functional consequences were characterized in vitro. Genotype-phenotype correlations were investigated in the wider kindred. Results The mutant IGSF1 protein (c.2318T>C, p.L773P) exhibited decreased plasma membrane expression in vitro due to impaired trafficking from the endoplasmic reticulum. Ten hemizygous males and 11 heterozygous females exhibited characteristic endocrine deficits. Ireland operates a TSH-based CH screening programme, which does not detect CeCH; therefore, genetic ascertainment preceded biochemical diagnosis of moderate CH in five of seven boys as well as their 75 year-old grandfather. Clinical features potentially attributable to hypothyroidism were variable; normal free T3 (FT3) and low/low normal reverse T3 (rT3) concentrations suggested that preferential deiodination of FT4 to FT3 may help maintain tissue euthyroidism in some individuals. However, neonatal jaundice, delayed speech or growth, and obesity were observed in seven subjects in whom diagnosis was delayed. Conclusions As observed with other IGSF1 mutations, p.L773P results in variably penetrant IGSF1 deficiency syndrome. Our observations emphasise the need for multi-generation genetic ascertainment in affected families, especially where TSH-based CH screening programmes may fail to detect CeCH at birth.

Published
2018

35. Alemtuzumab-induced thyroid dysfunction exhibits distinctive clinical and immunological features

Author

Pariani, Nadia, Willis, Mark, Muller, Ilaria, Healy, Sarah, Nasser, Taha, McGowan, Anne, Lyons, Greta, Jones, Joanne, Chatterjee, Krishna, Dayan, Colin, Robertson, Neil, Coles, Alasdair, Moran, Carla, Jones, Joanna [0000-0003-4974-1371], Chatterjee, Krishna [0000-0002-2654-8854], Coles, Alasdair [0000-0003-4738-0760], and Apollo - University of Cambridge Repository

Subjects
Thyroid, Adult, Male, Thyroiditis, Multiple Sclerosis, Middle Aged, Thyroid Diseases, Graves Disease, Young Adult, Disease Progression, Humans, Female, Alemtuzumab, Clinical Research Articles, Retrospective Studies
Abstract

Context Alemtuzumab, a highly effective treatment for multiple sclerosis (MS), predisposes to Graves disease (GD), with a reportedly indolent course. Objective To determine the type, frequency, and course of thyroid dysfunction (TD) in a cohort of alemtuzumab-treated patients with MS in the United Kingdom. Design Case records of alemtuzumab-treated patients who developed TD were reviewed. Results A total of 41.1% (102 out of 248; 80 female and 22 male) of patients developed TD, principally GD (71.6%). Median onset was 17 months (range 2 to 107) following the last dose, with the majority (89%) within 3 years. Follow-up data (range 6 to 251 months) were available in 71 case subjects, of whom 52 (73.2%) developed GD: 10 of these (19.2%) had fluctuating TD. All 52 patients with GD commenced antithyroid drugs (ATDs): 3 required radioiodine (RAI) due to ATD side effects, and drug therapy is ongoing in 2; of those who completed a course, 16 are in remission, 1 developed spontaneous hypothyroidism, and 30 (64%) required definitive or long-term treatment (RAI, n = 17; thyroidectomy, n = 5; and long-term ATDs, n = 8). Three cases of thyroiditis and 16 cases of hypothyroidism were documented: 5 with antithyroid peroxidase antibody positivity only, 10 with positive TSH receptor antibody (TRAb), and 1 of uncertain etiology. Bioassay confirmed both stimulating and blocking TRAb in a subset of fluctuating GD cases. Conclusions Contrary to published literature, we recorded frequent occurrence of GD that required definitive or prolonged ATD treatment. Furthermore, fluctuating thyroid status in GD and unexpectedly high frequency of TRAb-positive hypothyroidism suggested changing activity of TRAb in this clinical context; we have documented the existence of both blocking and stimulating TRAb in these patients., In a retrospective analysis of alemtuzumab-induced thyroid dysfunction, Graves disease with fluctuating status that was relatively refractory to treatment and anti-TSH receptor antibody–positive hypothyroidism was recorded.

Published
2018

38. Mutations in thyroid hormone receptor α1 cause premature neurogenesis and progenitor cell depletion in human cortical development

Author

Krieger, Teresa G, primary, Moran, Carla M, additional, Frangini, Alberto, additional, Visser, W Edward, additional, Schoenmakers, Erik, additional, Muntoni, Francesco, additional, Clark, Chris, additional, Gadian, David, additional, Chong, Wui K, additional, Kuczynski, Adam, additional, Dattani, Mehul, additional, Lyons, Greta, additional, Efthymiadou, Alexandra, additional, Varga-Khadem, Faraneh, additional, Simons, Benjamin D, additional, Chatterjee, Krishna, additional, and Livesey, Frederick J, additional

Published
2019
Full Text
View/download PDF

41. Homozygous resistance to thyroid hormone ?: can combined antithyroid drug and triiodothyroacetic acid treatment prevent cardiac failure?

Author

Moran, Carla, Habeb, Abdelhadi M, Kahaly, George J, Kampmann, Christoph, Hughes, Marina, Marek, Jan, Rajanayagam, Odelia, Kuczynski, Adam, Vargha-Khadem, Faraneh, Morsy, Mofeed, Offiah, Amaka C, Poole, Ken, Ward, Kate, Lyons, Greta, Halsall, David, Berman, Lol, Watson, Laura, Baguley, David, Mollon, John, Moore, Anthony T, Holder, Graham E, Dattani, Mehul, and Chatterjee, Krishna

Subjects
endocrine system, endocrine system diseases
Abstract

Resistance to thyroid hormone ? (RTH?) due to homozygous THRB defects is exceptionally rare, with only five kindreds reported worldwide. Cardiac dysfunction, which can be life-threatening, is recognized in the disorder. Here we describe the clinical, metabolic, ophthalmic, and cardiac findings in a 9-year-old boy harboring a biallelic THRB mutation (R243Q), along with biochemical, physiologic, and cardiac responses to carbimazole and triiodothyroacetic acid (TRIAC) therapy. The patient exhibits recognized features (goiter, nonsuppressed thyroid-stimulating hormone levels, upper respiratory tract infections, hyperactivity, low body mass index) of heterozygous RTH?, with additional characteristics (dysmorphic facies, winging of scapulae) and more markedly elevated thyroid hormone levels, associated with the homozygous form of the disorder. Notably, an older sibling with similar clinical features and probable homozygous RTH? had died of cardiac failure at age 13 years. Features of early dilated cardiomyopathy in our patient prompted combination treatment with carbimazole and TRIAC. Careful titration of therapy limited elevation in TSH levels and associated increase in thyroid volume. Subsequently, sustained reduction in thyroid hormones with normal TSH levels was reflected in lower basal metabolic rate, gain of lean body mass, and improved growth and cardiac function. A combination of antithyroid drug and TRIAC therapy may prevent thyrotoxic cardiomyopathy and its decompensation in homozygous or even heterozygous RTH? in which life-threatening hyperthyroid features predominate.

Published
2017

42. Comprehensive Screening of Eight Known Causative Genes in Congenital Hypothyroidism With Gland-in-Situ

Author

Nicholas, Adeline K, Serra, Eva G, Cangul, Hakan, Alyaarubi, Saif, Ullah, Irfan, Schoenmakers, Erik, Deeb, Asma, Habeb, Abdelhadi M, Almaghamsi, Mohammad, Peters, Catherine, Nathwani, Nisha, Aycan, Zehra, Saglam, Halil, Bober, Ece, Dattani, Mehul, Shenoy, Savitha, Murray, Philip G, Babiker, Amir, Willemsen, Ruben, Thankamony, Ajay, Lyons, Greta, Irwin, Rachael, Padidela, Raja, Tharian, Kavitha, Davies, Justin H, Puthi, Vijith, Park, Soo-Mi, Massoud, Ahmed F, Gregory, John W, Albanese, Assunta, Pease-Gevers, Evelien, Martin, Howard, Brugger, Kim, Maher, Eamonn R, Chatterjee, V Krishna K, Anderson, Carl A, Schoenmakers, Nadia, Schoenmakers, Erik [0000-0003-0674-8282], Maher, Eamonn [0000-0002-6226-6918], Chatterjee, Krishna [0000-0002-2654-8854], Schoenmakers, Nadia [0000-0002-0847-2884], and Apollo - University of Cambridge Repository

Subjects
Congenital Hypothyroidism/genetics, endocrine system, Genetic Screening, Iron-Binding Proteins/genetics, Receptors, Thyrotropin/genetics, Receptors, Thyrotropin, Original Articles, Autoantigens/genetics, Gene, R1, Iodide Peroxidase/genetics, Autoantigens, Iodide Peroxidase, Thyroglobulin, Pedigree, Phenotype, Thyroglobulin/genetics, Iron-Binding Proteins, Mutation, Congenital Hypothyroidism, Humans
Abstract

Context: Lower TSH screening cutoffs have doubled the ascertainment of congenital hypothyroidism (CH), particularly cases with a eutopically located gland-in-situ (GIS). Although mutations in known dyshormonogenesis genes or TSHR underlie some cases of CH with GIS, systematic screening of these eight genes has not previously been undertaken. Objective: Our objective was to evaluate the contribution and molecular spectrum of mutations in eight known causative genes (TG, TPO, DUOX2, DUOXA2, SLC5A5, SLC26A4, IYD, and TSHR) in CH cases with GIS. Patients, Design, and Setting: We screened 49 CH cases with GIS from 34 ethnically diverse families, using next-generation sequencing. Pathogenicity of novel mutations was assessed in silico. Results: Twenty-nine cases harbored likely disease-causing mutations. Monogenic defects (19 cases) most commonly involved TG (12), TPO (four), DUOX2 (two), and TSHR (one). Ten cases harbored triallelic (digenic) mutations: TG and TPO (one); SLC26A4 and TPO (three), and DUOX2 and TG (six cases). Novel variants overall included 15 TG, six TPO, and three DUOX2 mutations. Genetic basis was not ascertained in 20 patients, including 14 familial cases. Conclusions: The etiology of CH with GIS remains elusive, with only 59% attributable to mutations in TSHR or known dyshormonogenesis-associated genes in a cohort enriched for familial cases. Biallelic TG or TPO mutations most commonly underlie severe CH. Triallelic defects are frequent, mandating future segregation studies in larger kindreds to assess their contribution to variable phenotype. A high proportion (∼41%) of unsolved or ambiguous cases suggests novel genetic etiologies that remain to be elucidated., TG, TPO, DUOX2, DUOXA2, SLC5A5, SLC26A4, IYD and TSHR genes were screened in 49 cases of congenital hypothyroidism with eutopic gland-in-situ. 59% were solved including cases with triallelic mutations.

Published
2016

43. A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome

Author

Roche, Edna F., primary, McGowan, Anne, additional, Koulouri, Olympia, additional, Turgeon, Marc-Olivier, additional, Nicholas, Adeline K., additional, Heffernan, Emmeline, additional, El-Khairi, Ranna, additional, Abid, Noina, additional, Lyons, Greta, additional, Halsall, David, additional, Bonomi, Marco, additional, Persani, Luca, additional, Dattani, Mehul T., additional, Gurnell, Mark, additional, Bernard, Daniel J., additional, and Schoenmakers, Nadia, additional

Published
2018
Full Text
View/download PDF

44. Comprehensive screening of eight known causative genes in congenital hypothyroidism with gland-in-situ

Author

Nicholas, Adeline K., Serra, Eva G., Cangül, Hakan, Alyaarubi, Saif, Ullah, Irfan, Schoenmakers, Erik, Deeb, Asma, Habeb, Abdelhadi M., Almaghamsi, Mohammad, Peters, Catherine, Nathwani, Nisha, Aycan, Zehra, Bober, Ece, Dattani, Mehul, Shenoy, Savitha, Murray, Philip G., Babiker, Amir, Willemsen, Ruben, Thankamony, Ajay, Lyons, Greta, Irwin, Rachael, Padidela, Raja, Tharian, Kavitha, Davies, Justin H., Puthi, Vijith, Park, Soo-Mi, Massoud, Ahmed F., Gregory, John W., Albanese, Assunta, Pease-Gevers, Evelien, Martin, Howard, Brugger, Kim, Maher, Eamonn R., Chatterjee, V. Krishna K., Anderson, Carl A., Schoenmakers, Nadia, Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı., Sağlam, Halil, and C-7392-2019

Subjects
TPO protein, TG gene, Iodide peroxidase, Dual Oxidases, Congenital Hypothyroidism, Oxidoreductases, IYD gene, Autoantigens, Gene, Receptor gene, Thyroglobulin gene, Computer model, Phenomics, DUOX2 gene, Endocrinology & metabolism, Priority journal, Allele, Iodide organification defects, Goiter, Sequence analysis, TSHR gene, Pedigree, Phenotype, Iron-binding proteins, Cohort analysis, Human, TPO gene, Clinical article, Population, DNA sequence, Thyrotropin receptor, Guidelines, Thyroglobulin, Article, Autoantigen, Next generation sequencing, Genetic screening, Genetics, Humans, Pathogenicity, Genetic variation, Iron binding protein, Gene mutation, Receptors, thyrotropin, SLC5A5 gene, Congenital hypothyroidism, Japanese patients, DUOX2 mutations, Mutation, Genetic association, SLC26A4 gene, DUOXA2 gene, Dyshormonogenesis
Abstract

Context: Lower TSH screening cutoffs have doubled the ascertainment of congenital hypothyroidism (CH), particularly cases with a eutopically located gland-in-situ (GIS). Although mutations in known dyshormonogenesis genes or TSHR underlie some cases of CH with GIS, systematic screening of these eight genes has not previously been undertaken. Objective: Our objective was to evaluate the contribution and molecular spectrum of mutations in eight known causative genes (TG, TPO, DUOX2, DUOXA2, SLC5A5, SLC26A4, IYD, and TSHR) in CH cases with GIS. Patients, Design, and Setting:We screened 49 CH cases with GIS from 34 ethnically diverse families, using next-generation sequencing. Pathogenicity of novel mutations was assessed in silica. Results: Twenty-nine cases harbored likely disease-causing mutations. Monogenic defects (19 cases) most commonly involved TG (12), TPO (four), DUOX2 (two), and TSHR (one). Ten cases harbored triallelic (digenic) mutations: TG and TPO (one); SLC26A4 and TPO (three), and DUOX2 and TG (six cases). Novel variants overall included 15 TG, six TPO, and three DUOX2 mutations. Genetic basis was not ascertained in 20 patients, including 14 familial cases. Conclusions: The etiology of CH with GIS remains elusive, with only 59% attributable to mutations in TSHR or known dyshormonogenesis-associated genes in a cohort enriched for familial cases. Biallelic TG or TPO mutations most commonly underlie severe CH. Triallelic defects are frequent, mandating future segregation studies in larger kindreds to assess their contribution to variable phenotype. A high proportion (-41%) of unsolved or ambiguous cases suggests novel genetic etiologies that remain to be elucidated. Wellcome Trust European Commission - 100585/Z/12/Z - 095564/Z/11/Z - 098051 - WT091310 UK Research & Innovation (UKRI) Medical Research Council UK (MRC) - MC_UU_12012/5/B European Commission National Institute for Health Research (NIHR) - (NF-SI-0514-10176) NIHR (CL-2012-06-005)

Published
2016

47. A novel IGSF1 mutation in a large Irish kindred highlights the need for family screening in the IGSF1 deficiency syndrome

Author

Roche, Edna, primary, McGowan, Anne, additional, Koulouri, Olympia, additional, Turgeon, Marc-Olivier, additional, Nicholas, Adeline K, additional, Heffernan, Emmeline, additional, El-Khairi, Ranna, additional, Lyons, Greta, additional, Persani, Luca, additional, Dattani, Mehul T, additional, Gurnell, Mark, additional, Bernard, Daniel J, additional, and Schoenmakers, Nadia, additional

Published
2017
Full Text
View/download PDF

48. A novel IGSF1 mutation in a large Irish kindred highlights the need for systematic familial endocrine screening in the IGSF1 deficiency syndrome

Author

McGowan, Anne, primary, Roche, Edna, additional, Koulouri, Olympia, additional, Turgeon, Marc-Olivier, additional, Nicholas, Adeline K, additional, Heffernan, Emmeline, additional, El-Khairi, Ranna, additional, Lyons, Greta, additional, Persani, Luca, additional, Dattani, Mehul T, additional, Gurnell, Mark, additional, Bernard, Daniel J, additional, and Schoenmakers, Nadia, additional

Published
2017
Full Text
View/download PDF

49. Contrasting Phenotypes in Resistance to Thyroid Hormone Alpha Correlate with Divergent Properties of Thyroid Hormone Receptor α1 Mutant Proteins

Author

Moran, Carla, primary, Agostini, Maura, additional, McGowan, Anne, additional, Schoenmakers, Erik, additional, Fairall, Louise, additional, Lyons, Greta, additional, Rajanayagam, Odelia, additional, Watson, Laura, additional, Offiah, Amaka, additional, Barton, John, additional, Price, Susan, additional, Schwabe, John, additional, and Chatterjee, Krishna, additional

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results