Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia

@article{CliftonBligh1998MutationOT,
  title={Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia},
  author={Roderick John Clifton-Bligh and John M. Wentworth and Peter Heinz and M Crisp and Rhys John and John H. Lazarus and Marian Ludgate and Vengalil Krishna Chatterjee},
  journal={Nature Genetics},
  year={1998},
  volume={19},
  pages={399-401}
}
Congenital hypothyroidism occurs in one of every three to four thousand newborns, owing to complete or partial failure of thyroid gland development. Although thyroid hypoplasia has recently been associated with mutations in the thyrotropin (TSH) receptor, the cause of thyroid agenesis is unknown. Proteins including thyroid transcription factors 1 (TTF-1; refs 4, 5) and 2 (TTF-2; refs 6, 7) and Pax8 (refs 8, 9) are abundant in the developing mouse thyroid and are known to regulate genes… Expand
Thyroid defects due to Pax8 gene mutations.
  • G. Damante
  • Biology, Medicine
  • European journal of endocrinology
  • 1998
TLDR
The search for mutations of genes coding for TTF-1, T TF-2 and Pax8 in subjects with thyroid dysgenesis has revealed that defects in these factors are responsible for several cases of CH, revealing a complex picture suggestive for future development in the field. Expand
Mutations in the TTF2 Gene are Not a Common Finding in Patients with Isolated Cleft Palate and Choanal Atresia
TLDR
Results suggest that TTF-2 mutations are not a frequent cause of nonsyndromic defects involving palate and bucconasal membrane development. Expand
A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis.
TLDR
It is suggested that TTF-2 gene defects should also be considered in cases of syndromic CH without total athyreosis and indicate that human thyroid development can occur despite loss of T TF-2 function. Expand
A novel loss-of-function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate.
TLDR
The observations support the role of TTF-2 in both thyroid and palate development but suggest phenotypic heterogeneity of this syndromic form of CH, which may account for the absence of choanal atresia and bifid epiglottis in patients. Expand
A mouse model for hereditary thyroid dysgenesis and cleft palate
TLDR
It is shown that Titf2-null mutant mice exhibit cleft palate and either a sublingual or completely absent thyroid gland, which results in neonatal hypothyroidism that shows similarity to thyroid dysgenesis in humans. Expand
Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8.
TLDR
A novel mutation of PAX8 is described causing autosomal dominant transmission of CH with thyroid hypoplasia, giving further evidence that, contrary to the situation in knockout mice, haplo-insufficiency of Pax8 is a cause of CH in humans. Expand
Mutations in the gene encoding paired box domain (PAX8) are not a frequent cause of congenital hypothyroidism (CH) in Iranian patients with thyroid dysgenesis.
TLDR
The results indicate that the PAX8 mutation rate is very low and can only explain a minority of the cases, therefore, it is highly needed to further investigate the genes controlling development and function of thyroid. Expand
Aspectos genéticos do hipotireoidismo congênito
TLDR
Evidence suggests that mutations in transcription factors (TTF2, TTF1, and PAX-8) and TSH receptor gene could be responsible for the disease and the syndrome of resistance to thyroid hormone is rare, implies a hypothyroidism state for some tissues. Expand
A novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: evidence for phenotypic variability in mother and child.
TLDR
Findings confirm the important role of PAX8 in the development of the thyroid, but they indicate that PAX8 gene mutations may have a variable penetrance or expressivity. Expand
Development of the thyroid gland: lessons from congenitally hypothyroid mice and men
TLDR
Mouse knock‐outs have demonstrated that thyroid transcription factor‐1 (TTF‐1) and PAX8 are required for the survival and proliferation of thyroid follicular cell precursors, TTF‐2 for their downward migration and the thyrotropin receptor (TSHR) for post‐natal thyroid growth. Expand
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References

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Absence of mutations in the gene encoding thyroid transcription factor-1 (TTF-1) in patients with thyroid dysgenesis.
TLDR
The results rule out the presence of titf1 mutations, at least in the coding region, in the thyroid dysgenesis patients, and suggest that TTF-1 plays an important role in lung, brain, and pituitary development. Expand
A mouse model for hereditary thyroid dysgenesis and cleft palate
TLDR
It is shown that Titf2-null mutant mice exhibit cleft palate and either a sublingual or completely absent thyroid gland, which results in neonatal hypothyroidism that shows similarity to thyroid dysgenesis in humans. Expand
Mutations in the gene encoding thyroid transcription factor-1 (TTF-1) are not a frequent cause of congenital hypothyroidism (CH) with thyroid dysgenesis.
TLDR
The absence of mutations in the TTF-1 gene in the authors' samples indicates that the mutations in that gene are not a frequent cause of permanent congenital hypothyroidism. Expand
PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis
TLDR
Three point mutations in the coding region of PAX8 are reported in two sporadic patients and one familial case of TD, implicate PAX8 in the pathogenesis of TD and in normal thyroid development. Expand
Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland.
TLDR
By direct sequencing of the thyrotropin receptor gene, the substitution of threonine in place of a highly conserved alanine at position 553, in the fourth predicted transmembrane domain was identified, which resulted in extremely low expression at the cell surface as compared with the wild-type receptor. Expand
Genetic and linkage analysis of familial congenital hypothyroidism: exclusion of linkage to the TSH receptor gene
TLDR
The conclusion is that if mutation of the TSHR gene causes familial congenital hypothyroidism in humans, it affects only a small proportion of the cases. Expand
Genetic analysis of 29 kindreds with generalized and pituitary resistance to thyroid hormone. Identification of thirteen novel mutations in the thyroid hormone receptor beta gene.
TLDR
It is suggested that GRTH and PRTH are phenotypic variants of the same genetic disorder, whose clinical expression may be modulated by other non-mutation-related factors. Expand
Congenital hypothyroidism caused by mutations in the thyrotropin-receptor gene.
TLDR
A patient with congenital hypothyroidism and thyroid hypoplasia is described, due to two loss-of-function mutations in exon 10 of the thyrotropin-receptor gene. Expand
TTF‐2, a new forkhead protein, shows a temporal expression in the developing thyroid which is consistent with a role in controlling the onset of differentiation
TLDR
The cloning of TTF‐2 is reported, a DNA binding protein that recognizes sites on both Tg and TPO promoters that shows transient expression in the developing thyroid and anterior pituitary and suggests that this transcription factor plays the role in development of a negative controller of thyroid‐specific gene expression. Expand
Identification of a point mutation in the thyrotropin receptor of the hyt/hyt hypothyroid mouse.
TLDR
Functional consequences of the mutation appear to account for the observed TSH hyporesponsiveness and hypothyroidism in the hyt/hyt mouse. Expand
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