Abstract:
BACKGROUND:Congenital primary hypothyroidism (CH) is the most common endocrine disorder in neonates. METHODS:To identify novel genes, we performed whole exome sequencing (WES) in 6 patients with CH due to thyroid dysgenesis (TD). The potential effects of the most relevant variants were analyzed using in silico prediction tools. The most promising candidate gene, transient receptor potential channel 4-associated protein (TRPC4AP), was sequenced in 179 further patients with TD. Expression of TRPC4AP in human thyroid was investigated using RT-PCR. Trpc4ap- functional analysis was performed in Xenopus laevis using Morpholino (MO) antisense oligomers. RESULTS:WES identified a likely damaging mutation in TRPC4AP leading to a de novo stop codon p.Q552*. Targeted sequencing of TRPC4AP demonstrated gene variants with predicted damaging potential in 5 patients resulting each in an amino acid exchange (p.P706S, p.F729L, p.S777C, and p.N229S). We demonstrated that TRPC4AP is expressed in human thyroid gland tissue. Using Xenopus laevis, we showed that the volume of the tadpole thyroid anlage was reduced by 20% in Trpc4ap MO knockdowns compared to controls and by 41% in "Clustered Regularly Interspaced Short Palindromic Repeats"/Cas9-mediated gene knockout experiments. DISCUSSION:A recognized interaction of TRPC4AP and the NF-kappa-B-essential-modulator encoded by IKBKG gene was identified by IPA analysis. IKBKG plays a role in activation of the NF-κB-signaling pathway and regulates genes involved in proliferation and survival of thyrocytes and expression of key enzymes of thyroid hormone synthesis. CONCLUSION:TRPC4AP was identified as a novel candidate gene in TD, but further studies are needed to validate its role in thyroid function.
journal_name
Horm Res Paediatrjournal_title
Hormone research in paediatricsauthors
Choukair D,Eberle B,Vick P,Hermanns P,Weiss B,Paramasivam N,Schlesner M,Lornsen K,Roeth R,Klutmann C,Kreis J,Hoffmann GF,Pohlenz J,Rappold GA,Bettendorf Mdoi
10.1159/000507114subject
Has Abstractpub_date
2020-01-01 00:00:00pages
16-29issue
1eissn
1663-2818issn
1663-2826pii
000507114journal_volume
93pub_type
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章,评审
doi:10.1159/000488106
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND/AIMS:To evaluate effects of growth hormone (GH) treatment on behaviour and psychosocial characteristics in short-stature children. METHODS:99 referred prepubertal non-familiar short-stature children (32 GH deficiency; 67 idiopathic short stature) aged 3-11 years, randomized to fixed or individual GH doses a...
journal_title:Hormone research in paediatrics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1159/000322937
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更新日期:2017-01-01 00:00:00
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journal_title:Hormone research in paediatrics
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doi:10.1159/000313587
更新日期:2010-01-01 00:00:00
abstract::The hypothalamic-pituitary-thyroid axis is a common site of unintended, acquired disease either during or after the treatment of cancer. Children treated with external radiation therapy are at the highest risk for developing a thyroid-related late effect, but thyroid dysfunction and second primary thyroid neoplasms ca...
journal_title:Hormone research in paediatrics
pub_type: 杂志文章,评审
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abstract:BACKGROUND:The flare-up effect of GnRH analogues may cause transient uterine bleeding in girls affected with idiopathic central precocious puberty (ICPP). AIMS:To assess the incidence of endometrial bleeding and verify whether pretreatment with cyproterone acetate could counteract it. METHODS:Fifty-four girls affecte...
journal_title:Hormone research in paediatrics
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doi:10.1159/000308172
更新日期:2010-01-01 00:00:00
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journal_title:Hormone research in paediatrics
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journal_title:Hormone research in paediatrics
pub_type: 临床试验,杂志文章
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章
doi:10.1159/000357142
更新日期:2014-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章,评审
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更新日期:2019-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2018-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章
doi:10.1159/000442747
更新日期:2016-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章,评审
doi:10.1159/000368924
更新日期:2015-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章
doi:10.1159/000449057
更新日期:2016-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章,评审
doi:10.1159/000462973
更新日期:2017-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章
doi:10.1159/000355404
更新日期:2013-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章
doi:10.1159/000478696
更新日期:2017-01-01 00:00:00
abstract::Leydig cell testicular tumors are very rare in children. They can present as gonadotropin-independent precocious puberty due to excess androgen secretion. We report the case of an 8-year-old boy with isosexual precocity whose hormonal investigation showed luteinizing hormone-independent testosterone hypersecretion. Al...
journal_title:Hormone research in paediatrics
pub_type: 杂志文章
doi:10.1159/000358084
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章
doi:10.1159/000337218
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章
doi:10.1159/000271916
更新日期:2010-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章
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更新日期:2019-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章
doi:10.1159/000336923
更新日期:2012-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 临床试验,杂志文章
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更新日期:2014-01-01 00:00:00
abstract:BACKGROUND/AIMS:Autoimmune hypophysitis (AH) is a rare inflammatory disease of the pituitary gland causing varying degrees of hypopituitarism and/or sellar compression. Cranial MRI remains the best noninvasive tool to diagnose AH, although a diagnosis of certainty requires pituitary biopsy. The objective of this study ...
journal_title:Hormone research in paediatrics
pub_type: 杂志文章
doi:10.1159/000446912
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND/AIMS:Newborn screening protocols for congenital hypothyroidism (CH) vary as to whether a TSH or T4 algorithm or some combination is performed. We aimed to determine the 3-year clinical outcome of infants diagnosed with CH and screen-positive for CH using a 2-screen protocol that measures both T4 and TSH on a...
journal_title:Hormone research in paediatrics
pub_type: 临床试验,杂志文章
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更新日期:2019-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章,评审
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更新日期:2011-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type: 杂志文章
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更新日期:2014-01-01 00:00:00
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journal_title:Hormone research in paediatrics
pub_type:
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更新日期:2019-01-01 00:00:00
abstract::The thyroid hormone (TH) system plays a central role in central physiological processes of many species, including mammals and humans, ranging from growth and cell differentiation, energy metabolism, thermoregulation and phasing of hibernation or annual movements of migratory species, metamorphosis from larvae to adul...
journal_title:Hormone research in paediatrics
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
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pub_type: 杂志文章
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