In:
Hormone Research in Paediatrics, S. Karger AG, Vol. 82, No. 4 ( 2014), p. 252-260
Abstract:
〈 b 〉 〈 i 〉 Background/Aims: 〈 /i 〉 〈 /b 〉 This study aimed to clarify the frequency, phenotypes, and molecular spectrum of 〈 i 〉 DUOX2 〈 /i 〉 , 〈 i 〉 TPO 〈 /i 〉 , 〈 i 〉 TSHR, 〈 /i 〉 and 〈 i 〉 TG 〈 /i 〉 mutations in patients with congenital hypothyroidism (CH) with enlarged or normal-sized eutopic thyroid glands. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 The study cohort included 43 subjects from 41 unrelated families who had CH with eutopic thyroid glands. Mutation analyses of 〈 i 〉 DUOX2 〈 /i 〉 , 〈 i 〉 TPO 〈 /i 〉 , and 〈 i 〉 TSHR 〈 /i 〉 were performed. The functional capacities of novel missense variants of 〈 i 〉 DUOX2 〈 /i 〉 were verified by measuring H 〈 sub 〉 2 〈 /sub 〉 O 〈 sub 〉 2 〈 /sub 〉 generation in vitro. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Of the 43 subjects, 23 (53.5%) had sequence variants in at least one gene. Twelve different 〈 i 〉 DUOX2 〈 /i 〉 variants, including seven novel variants, were identified in 20 subjects. A functional analysis of the 〈 i 〉 DUOX2 〈 /i 〉 variants revealed that most variants, other than p.G206V and p.H678R, caused a significant reduction in H 〈 sub 〉 2 〈 /sub 〉 O 〈 sub 〉 2 〈 /sub 〉 generation. Therefore, 15 subjects harbored functionally deleterious 〈 i 〉 DUOX2 〈 /i 〉 variants. Of these, 5 subjects had transient CH, and 10 were found to have permanent CH. Sequence variants in 〈 i 〉 TSHR 〈 /i 〉 were identified in 5 subjects. One of the 43 subjects (2.3%) had sequence variants in two different genes. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 〈 i 〉 DUOX2 〈 /i 〉 variants are a relatively common cause of CH with normal-sized or enlarged eutopic thyroid glands. Variable phenotypes were associated with partial loss of the functional activity of 〈 i 〉 DUOX2 〈 /i 〉 variants.
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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