Mutations in MFSD8/CLN7 Are a Frequent Cause of Variant-Late Infantile Neuronal Ceroid Lipofuscinosis
Mutations in MFSD8/CLN7 Are a Frequent Cause of Variant-Late Infantile Neuronal Ceroid Lipofuscinosis
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DOI：
10.1002/humu.20975
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发表时间：
2009-03-01
期刊：
影响因子：
3.9
通讯作者：
Santorelli, Filippo M.
中科院分区：
文献类型：
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作者：
Aiello, Chiara;Terracciano, Alessandra;Santorelli, Filippo M.
神经性蜡样脂褐素增多症(NCL)是一组遗传异质性的神经退行性疾病。最近在来自土耳其的受影响儿童中发现了一种变异型晚期婴儿NCL(v-LINCL)的MFSD8/CLN7基因，这促使我们检查了该基因变异在意大利v-LINCL患者中的相对频率。我们确定了9名儿童在MFSD8/CLN7中存在11种不同的突变。有10个突变是新的，包括三个无义突变(p.Arg35Stop，p.Glu381Stop，p.Arg482Stop)，四个错义突变(p.Met1Thr，p.Gly52Arg，p.Thr294Lys，p.Pro447Leu)，两个剪接位点突变(c.863+3_4insT，c.863+1G>；C)，以及一个17bp的缺失，预测移码和蛋白质过早截断(c.627_643del17/p.Met209IlefsX3)。临床表型与土耳其v-LINCL病例相似，不受突变类型和位置以及预测残留基因产物长度的影响。除了识别MFSD8/CLN7的新变异外，这项研究还有助于更好地描述意大利NCL病例的分子特征，并将促进在这些家庭中进行医学遗传咨询。V-LINCL病例子集的存在没有任何已知NCL基因的突变，这表明进一步的遗传异质性。(C)2009年Wiley-Liss，Inc.
The neuronal ceroid lipofuscinoses (NCL) are a group of genetically heterogeneous neurodegenerative disorders. The recent identification of the MFSD8/CLN7 gene in a variant-late infantile form of NCL (v-LINCL) in affected children from Turkey prompted us to examine the relative frequency of variants in this gene in Italian patients with v-LINCL. We identified nine children harboring 11 different mutations in MFSD8/CLN7. Ten mutations were novel and included three nonsense (p.Arg35Stop, p.Glu381Stop, p.Arg482Stop), four missense (p.Met1Thr, p.Gly52Arg, p.Thr294Lys, p.Pro447Leu), two splice site mutations (c.863+3_4insT, c.863+1G>C), and a 17-bp deletion predicting a frameshift and premature protein truncation (c.627_643del17/p.Met209IlefsX3). The clinical phenotype, which was similar to that of the Turkish v-LINCL cases, was not influenced by type and location of the mutation nor the length of the predicted residual gene product. As well as identifying novel variants in MFSD8/CLN7, this study contributes to a better molecular characterization of Italian NCL cases, and will facilitate medical genetic counseling in such families. The existence of a subset of v-LINCL cases without mutations in any of the known NCL genes suggests further genetic heterogeneity. (C) 2009 Wiley-Liss, Inc.