In:
Hormone Research in Paediatrics, S. Karger AG, Vol. 82, No. 4 ( 2014), p. 261-271
Abstract:
〈 b 〉 〈 i 〉 Background/Aims: 〈 /i 〉 〈 /b 〉 Monocarboxylate transporter 8 (MCT8) is essential for thyroid hormone (TH) transport in the brain. Mutations in 〈 i 〉 MCT8 〈 /i 〉 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 〈 i 〉 MCT8 〈 /i 〉 and discuss the clinical findings. 〈 b 〉 〈 i 〉 Case Report and Results: 〈 /i 〉 〈 /b 〉 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 〈 i 〉 MCT8 〈 /i 〉 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. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Here 〈 b 〉 〈 /b 〉 we report 4 AHDS patients in unrelated Turkish families harboring novel 〈 i 〉 MCT8 〈 /i 〉 mutations. Despite the widely different mutations, the clinical phenotypes are very similar and findings support the progressive nature of AHDS.
Type of Medium:
Online Resource
ISSN:
1663-2818
,
1663-2826
Language:
English
Publisher:
S. Karger AG
Publication Date:
2014
detail.hit.zdb_id:
2540224-9
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