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MCT8 mutation analysis and identification of the first female with Allan-Herndon-Dudley syndrome due to loss of MCT8 expression.

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons50364

Jensen,  Lars Riff
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50604

Tzschach,  Andreas
Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50501

Ropers,  Hans Hilger
Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

Kuss,  Andreas Walter
Max Planck Society;

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Zitation

Frints, S. G. M., Lenzner, S., Bauters, M., Jensen, L. R., Van Esch, H., des Portes, V., et al. (2008). MCT8 mutation analysis and identification of the first female with Allan-Herndon-Dudley syndrome due to loss of MCT8 expression. European Journal of Human Genetics, 16(9), 1029-1037. doi:10.1038/ejhg.2008.66.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0010-800C-4
Zusammenfassung
Mutations in the thyroid monocarboxylate transporter 8 gene (MCT8/SLC16A2) have been reported to result in X-linked mental retardation (XLMR) in patients with clinical features of the Allan–Herndon–Dudley syndrome (AHDS). We performed MCT8 mutation analysis including 13 XLMR families with LOD scores >2.0, 401 male MR sibships and 47 sporadic male patients with AHDS-like clinical features. One nonsense mutation (c.629insA) and two missense changes (c.1A>T and c.1673G>A) were identified. Consistent with previous reports on MCT8 missense changes, the patient with c.1673G>A showed elevated serum T3 level. The c.1A>T change in another patient affects a putative translation start codon, but the same change was present in his healthy brother. In addition normal serum T3 levels were present, suggesting that the c.1A>T (NM_006517) variation is not responsible for the MR phenotype but indicates that MCT8 translation likely starts with a methionine at position p.75. Moreover, we characterized a de novo translocation t(X;9)(q13.2;p24) in a female patient with full blown AHDS clinical features including elevated serum T3 levels. The MCT8 gene was disrupted at the X-breakpoint. A complete loss of MCT8 expression was observed in a fibroblast cell-line derived from this patient because of unfavorable nonrandom X-inactivation. Taken together, these data indicate that MCT8 mutations are not common in non-AHDS MR patients yet they support that elevated serum T3 levels can be indicative for AHDS and that AHDS clinical features can be present in female MCT8 mutation carriers whenever there is unfavorable nonrandom X-inactivation.