分析GNAS1和重叠记录识别突变患者的父母起源零星奥尔布赖特遗传性骨营养不良和揭示了一个模型系统中观察到的影响在翻译和翻译信使RNA剪接变异。
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理查德SJ,威尔逊LC
分析GNAS1和重叠记录识别突变患者的父母起源零星奥尔布赖特遗传性骨营养不良和揭示了一个模型系统中观察到的影响在翻译和翻译信使RNA剪接变异。
J哼麝猫。2003年4月,72 (4):961 - 74。Epub 2003年3月6日。
- PubMed ID
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12624854 (在PubMed]
- 文摘
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奥尔布赖特遗传性骨营养不良(哦)是由杂合的GNAS1突变才会安静下来。有一个parent-of-origin效果。母亲般地派生与抗甲状旁腺激素相关突变通常称为“pseudohypoparathyroidism Ia型”。Paternally derived mutations are associated with AHO but usually normal hormone responsiveness, known as "pseudo-pseudohypoparathyroidism." These observations can be explained by tissue-specific GNAS1 imprinting. Regulation of the genomic region that encompasses GNAS1 is complex. At least three upstream exons that splice to exon 2 of GNAS1 and that are imprinted have been reported. NESP55 is exclusively maternally expressed, whereas exon 1A and XL alphas are exclusively paternally expressed. We set out to identify the parental origin of GNAS1 mutations in patients with AHO by searching for their mutation in the overlapping transcripts. This information would be of value in patients with sporadic disease, for predicting their endocrine phenotype and planning follow-up. In doing so, we identified mutations that resulted in nonsense-mediated decay of the mutant Gs alpha transcript but that were detectable in NESP55 messenger RNA (mRNA), probably because they lie within its 3' untranslated region. Analysis of the NESP55 transcripts revealed the creation of a novel splice site in one patient and an unusual intronic mutation that caused retention of the intron in a further patient, neither of which could be detected by analysis of the Gs alpha complementary DNA. This cluster of overlapping transcripts represents a useful model system in which to analyze the effects that mutant sequence has on mRNA-in particular, splicing-and the mechanisms of nonsense-mediated mRNA decay.