A novel heterozygous intronic mutation in POU1F1 is associated with combined pituitary hormone deficiency

作者：Takagi Masaki; Kamasaki Hotaka; Yagi Hiroko; Fukuzawa Ryuji; Narumi Satoshi; Hasegawa Tomonobu^*

来源：Endocrine Journal, 2017, 64(2): 229-234.

DOI：10.1507/endocrj.EJ16-0361

• POUlFI
• Short isoform
• Exon trapping
• Combined pituitary hormone deficiency

POU class 1 homeobox 1 (POUlFi) regulates pituitary cell- specific gene expression of somatotropes, lactotropes, and thyrotropes. In humans, two POUlF1 isoforms (long and short isoform), which are generated by the alternative use of the splice acceptor site for exon 2, have been identified. To date, more than 30 POU1F1 mutations in patients with combined pituitary hormone deficiency (CPHD) have been described. All POU1F1 variants reported to date affect both the short and long isoforms of the POUlF I protein; therefore, it is unclear at present whether a decrease in the function of only one of these two isoforms is sufficient for disease onset in humans. Here, we described a sibling case of CPHD carrying a heterozygous mutation in intron 1 of POU1F1. In vitro experiments showed that this mutation resulted in exon 2- skipping of only in the short isoform of POU1F1, while the long isoform remained intact. This result strongly suggests the possibility, for the first time, that isolated mutations in the short isoform of POU1Fi could be sufficient for induction of POU1Fl- related CPHD. This finding improves our understanding of the molecular mechanisms, and developmental course associated with mutations in POU1F1.

• 出版日期2017