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

Masaki Takagi, Hotaka Kamasaki, Hiroko Yagi, Ryuji Fukuzawa, Satoshi Narumi, Tomonobu Hasegawa

研究成果: Comment/debate査読

10 被引用数 (Scopus)

抄録

POU class 1 homeobox 1 (POU1F1) regulates pituitary cell-specific gene expression of somatotropes, lactotropes, and thyrotropes. In humans, two POU1F1 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 POU1F1 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 POU1F1 could be sufficient for induction of POU1F1-related CPHD. This finding improves our understanding of the molecular mechanisms, and developmental course associated with mutations in POU1F1.

本文言語English
ページ(範囲)229-234
ページ数6
ジャーナルEndocrine journal
64
2
DOI
出版ステータスPublished - 2017

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 内分泌学

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