Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation.

By E. Friesema, A. Grueters, H. Biebermann, H. Krude, A. von Moers, M. Reeser, T. Barrett, E. Mancilla, J. Svensson, M. Kester and 7 more. The Lancet, 2004

665 citations recorded by the source corpus.

Monocarboxylate transporter 8 (MCT8) is a thyroid hormone transporter, the gene of which is located on the X chromosome. We tested whether mutations in MCT8 cause severe psychomotor retardation and high serum triiodothyronine (T3) concentrations in five unrelated young boys. The coding sequence of MCT8 was analysed by PCR and direct sequencing of its six exons. In two patients, gene deletions of 2.4 kb and 24 kb were recorded and in three patients missense mutations Ala150Val, Arg171 stop, and Leu397Pro were identified. We suggest that this novel syndrome of X-linked psychomotor retardation is due to a defect in T3 entry into neurons through MCT8, resulting in impaired T3 action and metabolism.

Subfields: Endocrinology, Diabetes and Metabolism, Genetics

View Paper: https://www.semanticscholar.org/paper/db6469b46664f0864c4b773ad7781b0efd83d5dc

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In Endocrinology, Diabetes and Metabolism

1. G. Brent
2. J. Bernal

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1. J. Bernal
2. A. Halestrap
3. G. Brent

Citations in the corpus

• Thyroid hormone regulation of metabolism. (2014, background): “The MCT8 gene is located on the X chromosome (66, 84), and males with MCT8 gene mutations have neurologic abnormalities including dystonia and developmental delay, with progression to quadriplegia (18).”
• The monocarboxylate transporter family—Role and regulation (2012, background): “Here, a mutation in the MCT8 gene (located on the X chromosome) has been established and the lack of MCT8 activity in the brain prevents thyroid hormone uptake and thus normal brain development (29).”
• Thyroid hormone receptors in brain development and function (2007, background): “To what extent deficient transfer of T 3 from glial cells to neurons plays a part in this syndrome is a matter of debate”
• Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014, neutral): “These individuals have peripheral hypermetabolism and abnormal serum thyroid levels with elevated serum T3, low serum T4, and slightly high TSH (486,500,501).”
• The SLC16 gene family - structure, role and regulation in health and disease. (2013, background): “First, severe X-linked psychomotor retardation mutation can be caused by a mutation in the SLC16A2 gene (located on the X chromosome) which impairs thyroid hormone uptake into the brain leading to abnormal normal brain development (Friesema et al., 2004).”
• The monocarboxylate transporter family—Structure and functional characterization (2012, background): “Its importance in thyroid hormone transport has been confirmed by the identification of individuals with mutations in the MCT8 gene that exhibit major psychomotor retardation (42).”
• Chapter 6 Regulation And Contribution Of The Corticotropic, Melanotropic And Thyrotropic Axes To The Stress Response In Fishes (2009, background): “, 2005) and their critical role in thyroid hormone signalling has been unequivocally demonstrated in patients with severe pathologies that could be attributed to dysfunctional mutant transporters (Friesema et al., 2004; Jansen et al., 2008).”
• Mechanisms of thyroid hormone action. (2012, neutral): “When MCT8 was sequenced in these patients, inactivating mutations were identified in some individuals (54, 55).”