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2 results on '"Alies van Mullem"'

1. A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.

Author

Eleonora Porcu, Marco Medici, Giorgio Pistis, Claudia B Volpato, Scott G Wilson, Anne R Cappola, Steffan D Bos, Joris Deelen, Martin den Heijer, Rachel M Freathy, Jari Lahti, Chunyu Liu, Lorna M Lopez, Ilja M Nolte, Jeffrey R O'Connell, Toshiko Tanaka, Stella Trompet, Alice Arnold, Stefania Bandinelli, Marian Beekman, Stefan Böhringer, Suzanne J Brown, Brendan M Buckley, Clara Camaschella, Anton J M de Craen, Gail Davies, Marieke C H de Visser, Ian Ford, Tom Forsen, Timothy M Frayling, Laura Fugazzola, Martin Gögele, Andrew T Hattersley, Ad R Hermus, Albert Hofman, Jeanine J Houwing-Duistermaat, Richard A Jensen, Eero Kajantie, Margreet Kloppenburg, Ee M Lim, Corrado Masciullo, Stefano Mariotti, Cosetta Minelli, Braxton D Mitchell, Ramaiah Nagaraja, Romana T Netea-Maier, Aarno Palotie, Luca Persani, Maria G Piras, Bruce M Psaty, Katri Räikkönen, J Brent Richards, Fernando Rivadeneira, Cinzia Sala, Mona M Sabra, Naveed Sattar, Beverley M Shields, Nicole Soranzo, John M Starr, David J Stott, Fred C G J Sweep, Gianluca Usala, Melanie M van der Klauw, Diana van Heemst, Alies van Mullem, Sita H Vermeulen, W Edward Visser, John P Walsh, Rudi G J Westendorp, Elisabeth Widen, Guangju Zhai, Francesco Cucca, Ian J Deary, Johan G Eriksson, Luigi Ferrucci, Caroline S Fox, J Wouter Jukema, Lambertus A Kiemeney, Peter P Pramstaller, David Schlessinger, Alan R Shuldiner, Eline P Slagboom, André G Uitterlinden, Bijay Vaidya, Theo J Visser, Bruce H R Wolffenbuttel, Ingrid Meulenbelt, Jerome I Rotter, Tim D Spector, Andrew A Hicks, Daniela Toniolo, Serena Sanna, Robin P Peeters, and Silvia Naitza

Subjects
Genetics, QH426-470
Abstract

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.

Published
2013
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2. Psychomotor retardation caused by a defective thyroid hormone transporter: report of two families with different MCT8 mutations

Author

Ahmet, Anık, Simone, Kersseboom, Korcan, Demir, Gönül, Catlı, Uluç, Yiş, Ece, Böber, Alies, van Mullem, Ramona E A, van Herebeek, Semra, Hız, Ayhan, Abacı, and Theo J, Visser

Subjects
Male, Monocarboxylic Acid Transporters, Thyroid Hormones, Symporters, DNA Mutational Analysis, Mutation, Missense, Infant, Pedigree, Muscular Atrophy, Child, Preschool, Intellectual Disability, Mutation, Mental Retardation, X-Linked, Humans, Muscle Hypotonia, Child, Gene Deletion
Abstract

Monocarboxylate transporter 8 (MCT8) is essential for thyroid hormone (TH) transport in the brain. Mutations in MCT8 are associated with the Allan-Herndon-Dudley syndrome (AHDS), characterized by severe psychomotor retardation and altered serum thyroid parameters. Here we report two novel mutations in MCT8 and discuss the clinical findings.We describe 4 males with AHDS from two unrelated families varying in age from 1.5 to 11 years. All 4 patients presented with typical clinical signs of AHDS, including severe psychomotor retardation, axial hypotonia, lack of speech, diminished muscle mass, increased muscle tone, hyperreflexia, myopathic facies, high T3, low T4 and rT3, and normal/mildly elevated TSH levels. Comparison of patients at different ages suggests the progressive nature of AHDS. Genetic analyses identified a novel missense MCT8 mutation (p.G495A) in family 1 and a 2.8-kb deletion comprising exons 3 and 4 in family 2. Functional analysis of p.G495A revealed impaired TH transport varying from 20 to 85% depending on the cell context.Here we report 4 AHDS patients in unrelated Turkish families harboring novel MCT8 mutations. Despite the widely different mutations, the clinical phenotypes are very similar and findings support the progressive nature of AHDS.

Published
2014

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