Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency.
Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency.
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DOI：
10.1002/emmm.201303573
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发表时间：
2014-03
影响因子：
11.1
通讯作者：
Perez-Jurado, Luis A. '
中科院分区：
文献类型：
--
作者：
Argente, Jesus;Flores, Raquel;Gutierrez-Arumi, Armand;Verma, Bhupendra;Martos-Moreno, Gabriel A.;Cusco, Ivon;Oghabian, Ali;Chowen, Julie A.;Frilander, Mikko J.;Perez-Jurado, Luis A. '
大量孤立性生长激素缺乏症的分子基础尚不清楚。我们描述了三个姐妹，由于RNPC3基因的双等位突变而导致严重的孤立性生长激素缺乏和垂体发育不良，RNPC3基因编码U11/U12小核核糖核蛋白(SnRNP)形成和U12型内含子剪接所需的微小剪接体蛋白。我们在患者细胞中发现了U11/U12di-SnRNP的形成和多个U12型内含子的剪接异常。有缺陷的转录本包括激素前体转换酶SPCS2和SPCS3以及肌动蛋白相关的ARPC5L基因，这些基因是生长激素限制性功能障碍的候选基因。已报道的家族性生长激素缺乏的新机制表明，微小剪接体的一般mRNA处理缺陷可以导致非常窄的组织特异性后果。学科类别遗传学，基因治疗的遗传病；代谢
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. Subject Categories Genetics, Gene Therapy ' Genetic Disease; Metabolism
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影响因子：
64.5
作者：
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通讯作者：
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通讯作者：
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