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首页> 外文期刊>BMC Genomics >Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency
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Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency

机译：LARP7缺乏症的Alazami综合征患者端粒维持受损

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Background Loss of function in genes required for telomere maintenance result in disorders known as telomeropathies, which are characterized by a pattern of symptoms including generalized and specific lymphocytopenias as well as very short telomere length and disease anticipation. Methods Because human LARP7 is the most likely ortholog of the Tetrahymena p65 protein, which is required for telomerase activity in that organism, we investigated the effects of LARP7 silencing in human cells as well as in two distinct families with Alazami syndrome (loss of function of LARP7). Results Depletion of LARP7 caused a reduction in telomerase enzymatic activity and progressively shorter telomeres in human cancer cell lines. Alazami syndrome patients from two separate cohorts exhibited very short lymphocyte telomeres. Further, wild-type offspring of LARP7 mutant individuals also had very short telomeres, comparable to what is observed in telomerase (hTERT) mutant cohorts. Conclusions Together, these experiments demonstrate that in addition to the readily apparent developmental disorder associated with LARP7 deficiency, an underlying telomeropathy exists even in unaffected siblings of these individuals.
机译：背景端粒维持所需基因的功能丧失导致称为端粒病的疾病，其特征在于症状的模式，包括全身性和特异性淋巴细胞减少以及端粒长度很短和疾病预期。方法由于人LARP7是四膜虫p65蛋白的最可能直系同源基因，是该生物中端粒酶活性所必需的直系同源物，因此我们研究了LARP7沉默在人细胞以及Alazami综合征的两个不同家族中的作用（功能丧失LARP7）。结果LARP7的耗尽导致人类癌细胞系中端粒酶活性降低，端粒逐渐缩短。来自两个不同队列的Alazami综合征患者表现出非常短的淋巴细胞端粒。此外，与在端粒酶（hTERT）突变人群中观察到的结果相当，LARP7突变体个体的野生型后代也具有非常短的端粒。结论总之，这些实验表明，除了与LARP7缺乏相关的显而易见的发育障碍外，潜在的端粒病甚至存在于这些个体的未患病兄弟姐妹中。

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