Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency

Jesús Argente, Raquel Flores, Armand Gutiérrez-Arumí, Bhupendra Verma, Gabriel Á Martos-Moreno, Ivon Cuscó, Ali Oghabian, Julie A. Chowen, Mikko J. Frilander, Luis A. Pérez-Jurado

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80 Citations (Scopus)


The molecular basis of a significant number of cases of isolated growth hormone deficiency remains unknown. We describe three sisters affected with severe isolated growth hormone deficiency and pituitary hypoplasia caused by biallelic mutations in the RNPC3 gene, which codes for a minor spliceosome protein required for U11/U12 small nuclear ribonucleoprotein (snRNP) formation and splicing of U12-type introns. We found anomalies in U11/U12 di-snRNP formation and in splicing of multiple U12-type introns in patient cells. Defective transcripts include preprohormone convertases SPCS2 and SPCS3 and actin-related ARPC5L genes, which are candidates for the somatotroph-restricted dysfunction. The reported novel mechanism for familial growth hormone deficiency demonstrates that general mRNA processing defects of the minor spliceosome can lead to very narrow tissue-specific consequences.

Original languageEnglish
Pages (from-to)299-306
Number of pages8
JournalEMBO Molecular Medicine
Issue number3
Publication statusPublished or Issued - Mar 2014
Externally publishedYes


  • Pituitary hypoplasia
  • U12-type introns
  • mRNA splicing

ASJC Scopus subject areas

  • Molecular Medicine

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