Title: MCT8 mutation analysis and identification of the first female with Allan-Herndon-Dudley syndrome due to loss of MCT8 expression
Authors: Frints, Suzanna Gerarda Maria ×
Lenzner, Steffen
Bauters, Marijke
Jensen, Lars Riff
Van Esch, Hilde
des Portes, Vincent
Moog, Ute
Macville, Merryn Victor Erik
van Roozendaal, Kees
Schrander-Stumpel, Constance Theresia Rimbertha Maria
Tzschach, Andreas
Marynen, Peter
Fryns, Jean-Pierre
Hamel, Ben
van Bokhoven, Hans
Chelly, Jamel
Beldjord, Chérif
Turner, Gillian
Gecz, Jozef
Moraine, Claude
Raynaud, Martine
Ropers, Hans Hilger
Froyen, Guido
Kuss, Andreas Walter #
Issue Date: Sep-2008
Publisher: Karger
Series Title: European Journal of Human Genetics vol:16 issue:9 pages:1029-1037
Abstract: 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.European Journal of Human Genetics advance online publication, 9 April 2008; doi:10.1038/ejhg.2008.66.
ISSN: 1018-4813
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Clinical Genetics Section (-)
Human Genome Laboratory
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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