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

Jesus Argente, Raquel Flores, Armand Gutierrez-Arumi, Bhupendra Verma, Gabriel A. Martos-Moreno, Ivon Cusco, Ali Oghabian, Julie A. Chowen, Mikko J. Frilander, Luis A. ' Perez-Jurado

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review


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.
TidskriftEMBO molecular medicine
Sidor (från-till)299-306
Antal sidor8
StatusPublicerad - mar 2014
MoE-publikationstypA1 Tidskriftsartikel-refererad


  • 1182 Biokemi, cell- och molekylärbiologi

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