Disease relevance of TBX19

• We investigated by immunohistochemistry and in situ hybridization the expression of TPIT in normal human anterior pituitary tissue and in several types of human pituitary adenomas (n = 52) [1].
• In situ hybridization studies demonstrated that TPIT transcripts were coexpressed with POMC mRNA in both secreting and silent corticotroph adenomas, and in normal corticotrophs, whereas TPIT mRNA was not detectable in other types of pituitary adenomas [1].
• Expression of Tpit and Pitx1 genes in most carcinoids suggests that some aspects of the pituitary corticotroph phenotype may belong to general carcinoid differentiation [2].
• CONCLUSIONS: Aberrant TPIT is unlikely to play a role in corticotroph tumoral trasformation, ie, Cushing's disease, as the entire coding sequence is expressed without any mutation by human pituitary ACTH-secreting adenomas [3].

High impact information on TBX19

• We compared the clinical and biological phenotype of the 17 IAD patients carrying a TPIT mutation with the 10 IAD patients with normal TPIT-coding sequences [4].
• TPIT mutations are associated with early-onset, but not late-onset isolated ACTH deficiency [5].
• Recently, mutations in the TPIT gene, a T-box factor selectively expressed in developing corticotroph cells, have been found in cases of early-onset IAD [5].
• Fifteen single nucleotide polymorphisms that were not predicted to change the TPIT transcript were also detected [5].
• METHODS: Genomic DNA was extracted and the sequences of the 8 TPIT exons and their intron/exon junctions were determined by automated sequencing [5].

Biological context of TBX19

• This stop codon probably leads to loss of TPIT function by nonsense-mediated mRNA decay, as it does for other TPIT nonsense mutations [6].
• Furthermore, using analysis of haplotypes among trios (n=219) by transmission disequilibrium test (TDT), a strong tendency for over-transmission of a haplotype C-G-A was found a t the TBX19 locus, among suicide attempters with high angry hostility scores [7].
• We present a neonate with the diagnosis of congenital early onset isolated ACTH deficiency (IAD) associated with a loss of POMC function as a result of a missense mutation in the TPIT gene [8].
• One of those relationships was confirmed in the replication sample (P=0.0052, Bonferroni correction), indicating that genetic variation at the human T-box 19 (TBX19) locus is related to the personality trait angry hostility [7].

Associations of TBX19 with chemical compounds

• Low estriol levels in the maternal triple-marker screen as a predictor of isolated adrenocorticotropic hormone deficiency caused by a new mutation in the TPIT gene [6].

Regulatory relationships of TBX19

• BACKGROUND: TPIT is a recently identified transcription factor specific to proopiomelanocortin (POMC)-expressing cells within the pituitary and plays a pivotal role in the embryonal development of POMC lineage [3].

Other interactions of TBX19

• A neonatal form of isolated ACTH deficiency frequently associated with Tpit gene mutations [9].

Analytical, diagnostic and therapeutic context of TBX19

• Identification of TPIT gene mutations as the principal molecular cause of neonatal IAD permits prenatal diagnosis for families at risk for the purpose of early glucocorticoid replacement therapy [4].
• Unlike POMC, TPIT was not up-regulated by adrenalectomy in rats and did not seem down-regulated in the normal pituitary adjacent to human corticotroph microadenomas [1].
• A subgroup of these lesions were examined by RT-PCR and among eight adenomas with typical "honeycomb Golgi" one case expressed both Tpit and SF-1, probably due to contamination with normal pituitary and another expressed neither Tpit nor SF-1 [10].

References