Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what money
Authors and funding
29 authors.
Stefan GroenewegAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Erasmus University Rotterdam, 3015 GD Rotterdam, the Netherlands.ORCID 0000-0001-6879-7392
Ferdy S van GeestAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Erasmus University Rotterdam, 3015 GD Rotterdam, the Netherlands.ORCID 0000-0002-6960-5775
Floor van der MostAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Erasmus University Rotterdam, 3015 GD Rotterdam, the Netherlands.ORCID 0009-0007-6727-3432
Paolo AlfieriUnit of Child Neuropsychiatry, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.ORCID 0000-0003-2197-9417
Andrew J BauerThe Thyroid Center, Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Enrico BertiniUnit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.ORCID 0000-0001-9276-4590
Marco CappaUnit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.ORCID 0000-0001-5647-7519
Nurullah ÇelikDivision of Paediatric Endocrinology, Department of Child Health and Diseases, Sivas Cumhuriyet University Faculty of Medicine, 58140 Sivas, Turkey.ORCID 0000-0003-1583-6807
Irenaeus F M de CooDepartment of Paediatric Neurology, Erasmus Medical Center, Erasmus University Rotterdam, 3015 GD Rotterdam, the Netherlands.ORCID 0000-0003-0533-7422
Anna Dolcetta-CapuzzoAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Erasmus University Rotterdam, 3015 GD Rotterdam, the Netherlands.
Jorge L GranadilloDepartment of Paediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.ORCID 0000-0003-4243-204X
Lies H HoefslootDepartment of Clinical Genetics, Erasmus Medical Center, Erasmus University Rotterdam, 3015 GD Rotterdam, the Netherlands.ORCID 0009-0000-3444-9955
Vera M KalscheuerResearch Group Development and Disease, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.ORCID 0000-0001-6898-3259
Marieke M van der KnoopDepartment of Paediatric Neurology, Erasmus Medical Center, Erasmus University Rotterdam, 3015 GD Rotterdam, the Netherlands.ORCID 0000-0002-8721-6300
Kyle P McNerneyDepartment of Paediatrics, Division of Endocrinology, Diabetes, and Metabolism, Washington University School of Medicine, St Louis, MO 63110, USA.
Laura PaoneUnit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
Robin P PeetersAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Erasmus University Rotterdam, 3015 GD Rotterdam, the Netherlands.ORCID 0000-0001-7732-9371
Catherine PetersDepartment of Paediatric Endocrinology, Great Ormond Street Hospital for Children, London WC1N 3JH, UK.
Markus SchuelkeDepartment or Neuropediatrics, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.ORCID 0000-0003-2824-3891
Ulrich SchweizerInstitut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, D-53115 Bonn, Germany.ORCID 0000-0003-1380-4780
Jennifer E SpragueDepartment of Paediatrics, Division of Endocrinology, Diabetes, and Metabolism, Washington University School of Medicine, St Louis, MO 63110, USA.ORCID 0000-0003-1315-5119
A S Paul van TrotsenburgDepartment of Paediatric Endocrinology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.ORCID 0000-0002-9677-7441
Nina-Maria WilpertDepartment or Neuropediatrics, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.ORCID 0000-0001-9453-8335
Ginevra ZanniUnit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.ORCID 0000-0002-6367-1843
Laura J C M van ZutvenDepartment of Clinical Genetics, Erasmus Medical Center, Erasmus University Rotterdam, 3015 GD Rotterdam, the Netherlands.ORCID 0000-0002-1092-2610
W Edward VisserAcademic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Erasmus University Rotterdam, 3015 GD Rotterdam, the Netherlands.ORCID 0000-0002-5248-863X
Funding
Eurostars program E113377Netherlands Organisation for Health Research and Development 113303005Sherman Foundation
6 · The paper itself
Abstract
contextMonocarboxylate transporter (MCT) 8 facilitates thyroid hormone (TH) transport across the blood-brain barrier. Pathogenic variants in SLC16A2 cause MCT8 deficiency (Allan-Herndon-Dudley syndrome), characterized by intellectual and motor disability and abnormal thyroid function tests. MCT8 deficiency typically affects males due to its X-linked inheritance.
objectiveHere, we report 8 female patients with heterozygous pathogenic variants in SLC16A2 who presented with variable neurocognitive impairment, behavioral problems, and TH function abnormalities.
methodsWe performed X-chromosome inactivation studies in female patients in whom heterozygous pathogenic variants in SLC16A2 were identified. The effect of SLC16A2 variants on TH transport was assessed in transfected cells and patient-derived fibroblasts.
resultsIn all patients (mean age 8.6 years; range, 2.3-25 years) routine care genetic analyses identified heterozygous variants in SLC16A2 (p.(R445C), p.(N193I), p.(G276R), t(X;20), resulting in a breakpoint in intron 1, t(X;19), resulting in a breakpoint in SLC16A2, p.(I562Sfs566*), p.(G221R)). All missense variants showed substantially reduced MCT8-mediated TH uptake in transiently transfected cells. X-chromosome inactivation studies in patient cells showed skewed X-inactivation in all 7 evaluated individuals. In 5 out of 7 evaluated cases, MCT8-mediated 3,5,3'-triiodothyronine (T3) uptake in patient-derived fibroblasts was impaired to a similar degree as in fibroblasts derived from male patients with MCT8 deficiency.
conclusionFemale patients with heterozygous pathogenic variants in SLC16A2 and skewed X-chromosome inactivation may present with variable neuro(psycho)logical, behavioral, and thyroid function test abnormalities. Female patients presenting with neurocognitive impairment and abnormal TH function tests (low free thyroxine and/or high total T3 concentrations) should be tested for genetic variants in SLC16A2.
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.
MCT8 Deficiency in Females. · full record | OpenQuestion