期刊
EMBO MOLECULAR MEDICINE
卷 6, 期 3, 页码 299-306出版社
WILEY-BLACKWELL
DOI: 10.1002/emmm.201303573
关键词
pituitary hypoplasia; mRNA splicing; U12-type introns
资金
- Spanish Ministry of Science and Innovation
- European FEDER [FIS PI10/0747, FIS PI10/2512]
- Network Center for Biomedical Research on Obesity and Nutrition (CIBERobn) Instituto Carlos III, Fundacion Endocrinologia y Nutricion
- Academy of Finland
- Sigrid Juselius Foundation
- Network Center for Biomedical Research on Rare Diseases (CIBERER) Instituto Carlos III, Fundacion Endocrinologia y Nutricion
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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