Partial deficiency of Thyroid transcription factor 1 produces predominantly neurological defects in humans and mice

摘要: Three genes, TTF1, TTF2, and PAX8, involved in thyroid gland development migration have been identified. Yet systematic screening for defects these genes dysgenesis gave essentially negative results. In particular, no TTF1 gene were found 76 individuals with even though a deletion of this the mouse results lung agenesis defective diencephalon. We report 6-year-old boy predominant dyskinesia, neonatal respiratory distress, mild hyperthyrotropinemia. One allele his had guanidine inserted into codon 86 producing nonsense protein 407, rather than 371, amino acids. The mutant did not bind to its canonical cis-element or transactivate reporter driven by thyroglobulin promoter, natural target TTF1. Failure interfere binding transactivation functions wild-type suggested that syndrome was caused haploinsufficiency. This confirmed mice heterozygous Ttf1 deletion, heretofore considered be normal. Compared littermates, Ttf1(+/-) poor coordination significant elevation serum thyrotropin. Therefore, haploinsufficiency predominantly neurological phenotype secondary