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

EMBO Mol Med 2014 03 30;6(3):299-306. Epub 2014 Jan 30.

Departments of Endocrinology and Pediatrics, Hospital Infantil Universitario Niño Jesús Universidad Autónoma de Madrid, Madrid, Spain.

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.

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http://dx.doi.org/10.1002/emmm.201303573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3958305PMC
March 2014
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