Novel mutations causing biotinidase deficiency in individuals identified by newborn screening in Michigan including an unique intronic mutation that alters mRNA expression of the biotinidase gene
Novel mutations causing biotinidase deficiency in individuals identified by newborn screening in Michigan including an unique intronic mutation that alters mRNA expression of the biotinidase gene
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DOI：
10.1016/j.ymgme.2014.04.002
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发表时间：
2014-07-01
影响因子：
3.8
通讯作者：
Wolf, B.
中科院分区：
文献类型：
--
作者：
Li, H.;Spencer, L.;Wolf, B.
生物素酶缺乏症(BD)是一种常染色体隐性遗传病，导致维生素生物素不能循环利用。生物素酶缺乏的人如果不接受生物素治疗，可能会出现神经和皮肤症状。到目前为止，已经报道了超过165个生物素酶基因(BID)的突变。基本上，除了c.1330G>；C(p.D444H)突变外，所有突变导致的酶活性低于平均正常血清酶活性的10%(严重的生物素酶缺乏)，该突变导致酶具有平均正常血清活性的50%，并且如果第二个等位基因上存在严重的生物素酶缺乏突变，则会导致部分生物素酶缺乏(平均正常血清生物素酶活性的10-30%)。我们现在报告了从1988年到2012年底在密歇根州新生儿筛查中发现的10名儿童中的8个新突变。有趣的是，一个内含子突变，c.310-15delT，通过定量实时逆转录聚合酶链式反应(qRT-PCR)导致BM mRNA表达下调近两倍。这是Bid基因内含子突变的第一个报告，并证明了它通过改变mRNA表达对酶活性的影响。这项研究确定了另外三个可能导致部分生物素酶缺乏症的突变。这些结果强调了对Biotinidase缺乏症患者进行Bid全基因测序的重要性，以更好地了解未来基因和表型的相关性。(C)2014 Elsevier Inc.保留所有权利。
Biotinidase deficiency (BD) is an autosomal recessive disorder resulting in the inability to recycle the vitamin biotin. Individuals with biotinidase deficiency can develop neurological and cutaneous symptoms if they are not treated with biotin. To date, more than 165 mutations in the biotinidase gene (BID) have been reported. Essentially all the mutations result in enzymatic activities with less than 10% of mean normal serum enzyme activity (profound biotinidase deficiency) with the exception of the c.1330G>C (p.D444H) mutation, which results in an enzyme having 50% of mean normal serum activity and causes partial biotinidase deficiency (10-30% of mean normal serum biotinidase activity) if there is a mutation for profound biotinidase deficiency on the second allele. We now reported eight novel mutations in ten children identified by newborn screening in Michigan from 1988 to the end of 2012. Interestingly, one intronic mutation, c.310-15delT, results in an approximately two-fold down-regulation of BM mRNA expression by Quantitative real-time reverse-transcription PCR (qRT-PCR). This is the first report of an intronic mutation in the BID gene with demonstration of its effect on enzymatic activity by altering mRNA expression. This study identified three other mutations likely to cause partial biotinidase deficiency. These results emphasize the importance of full gene sequencing of BID on patients with biotinidase deficiency to better understand the genotype and phenotype correlation in the future. (C) 2014 Elsevier Inc. All rights reserved.