Argente, JesúsFlores, RaquelGutiérrez Arumi, Armand, 1980-Verma, BhupendraMartos Moreno, Gabriel A.Cuscó Martí, Ivon, 1973-Oghabian, AliChowen, Julie A.Frilander, Mikko J.Pérez Jurado, Luis Alberto2015-06-052015-06-052014Argente J, Flores R, Gutiérrez-Arumi A, Verma B, Martos-Moreno GA, Cuscó I et al. Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency. EMBO Molecular Medicine. 2014;6:299-306. DOI 10.1002/emmm.2013035731757-4676http://hdl.handle.net/10230/23738The 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.application/pdfeng© 2014 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Hormones pituïtàriesRNA missatgerProteïnesinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1002/emmm.201303573MRNA splicingPituitary hypoplasiaU12-type intronsinfo:eu-repo/semantics/openAccess