RT Journal Article
T1 Mutations of the thyroid hormone transporter MCT8 cause prenatal brain bamage and persistent hypomyelination
A1 López Espíndola, Daniela
A1 Morales Bastos, Carmen
A1 Grijota Martínez, María Carmen
A1 Liao, Xiao-Hui
A1 Lev, Dorit
A1 Sugo, Ella
A1 Verge, Charles F.
A1 Refetoff, Samuel
A1 Bernal, Juan
A1 Guadaño Ferraz, Ana
AB Context: Mutations in the MCT8 (SLC16A2) gene, encoding a specific thyroid hormone transporter, cause an X-linked disease with profound psychomotor retardation, neurological impairment, and abnormal serum thyroid hormone levels. The nature of the central nervous system damage is unknown. Objective: The objective of the study was to define the neuropathology of the syndrome by analyzing brain tissue sections from MCT8-deficient subjects. Design: We analyzed brain sections from a 30th gestational week male fetus and an 11-year-old boy and as controls, brain tissue from a 30th and 28th gestational week male and female fetuses, respectively, and a 10-year-old girl and a 12-year-old boy. Methods: Staining with hematoxylin-eosin and immunostaining for myelin basic protein, 70-kDa neurofilament, parvalbumin, calbindin-D28k, and synaptophysin were performed. Thyroid hormone determinations and quantitative PCR for deiodinases were also performed. Results: The MCT8-deficient fetus showed a delay in cortical and cerebellar development and myelination, loss of parvalbumin expression, abnormal calbindin-D28k content, impaired axonal maturation, and diminished biochemical differentiation of Purkinje cells. The 11-year-old boy showed altered cerebellar structure, deficient myelination, deficient synaptophysin and parvalbumin expression, and abnormal calbindin-D28k expression. The MCT8-deficient fetal cerebral cortex showed50%reduction of thyroid hormones and increased type 2 deiodinase and decreased type 3 deiodinase mRNAs. Conclusions: The following conclusions were reached: 1) brain damage in MCT8 deficiency is diffuse, without evidence of focal lesions,andpresent from fetal stages despite apparent normality at birth; 2) deficient hypomyelination persists up to 11 years of age; and 3) the findings are compatible with the deficient action of thyroid hormones in the developing brain caused by impaired transport to the target neural cells.
PB Oxford University Press
SN 0021-972X
YR 2014
FD 2014
LK https://hdl.handle.net/20.500.14352/92576
UL https://hdl.handle.net/20.500.14352/92576
LA eng
NO López-Espíndola, Daniela, et al. «Mutations of the Thyroid Hormone Transporter MCT8 Cause Prenatal Brain Damage and Persistent Hypomyelination». The Journal of Clinical Endocrinology & Metabolism, vol. 99, n.o 12, diciembre de 2014, pp. E2799-804. https://doi.org/10.1210/jc.2014-2162.
NO Ministerio de Economía y Competitividad (España)
NO Instituto de Salud Carlos III
NO National Institutes of Health 
NO Sherman Family
DS Docta Complutense
RD 6 abr 2025