A novel homozygous GALC mutation: very early onset and rapidly progressive Krabbe disease.
A novel homozygous GALC mutation: very early onset and rapidly progressive Krabbe disease.
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DOI：
10.1016/j.gene.2012.12.040
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发表时间：
2013-03
期刊：
影响因子：
3.5
通讯作者：
F. Kardaş;A. Uzak;M. A. Hossain;N. Sakai;M. Canpolat;A. Yıkılmaz
中科院分区：
文献类型：
--
作者：
F. Kardaş;A. Uzak;M. A. Hossain;N. Sakai;M. Canpolat;A. Yıkılmaz
克拉伯病尚无明确的基因型-表型相关性。因此，识别新突变及其相关表型对于预测疾病的预后非常重要。本研究的目的是确定克拉伯病家族中的致病突变。经过临床评估并怀疑克拉伯病后，对半乳糖脑苷酶活性进行了分析，并进行了 GALC 基因突变分析。半乳糖脑苷脂酶活性为 0.01nmol/mg/h 蛋白质（正常范围为 0.8-4）。为了进一步研究，通过桑格测序对 GALC 基因的 17 个外显子进行突变筛查。发现了一个新的纯合突变 c.727delT (p.S243QfsX7)。在这项研究中，我们展示了土耳其近亲家庭中的临床发现以及新的 GALC 突变。尽管克拉伯病各基因型和表型之间的关系尚未完全阐明，但准确的遗传家系研究有助于克拉伯病的遗传咨询随访和治疗。此外，识别新的突变以阐明其临床重要性、评估疾病的预后以及向受影响的家庭建议产前诊断或植入前遗传学诊断也很重要。
A clear cut genotype–phenotype correlation for Krabbe disease is not available. Therefore, it is important to identify new mutations and their associated phenotypes to predict the prognosis of the disease. The aim of this study is to identify the causative mutation(s) in a family with Krabbe disease. After a clinical evaluation and suspicion of Krabbe disease galactocerebrosidase activity was analyzed and GALC gene mutation analysis was performed. The galactocerebrosidase enzyme activity was 0.01nmol/mg/h protein (normal range 0.8–4). For further investigation mutation screening was performed by Sanger sequencing across the 17 exons of GALC gene. A novel homozygous mutation c.727delT (p.S243QfsX7) was found. In this study we present the clinical findings along with a novel GALC mutation in a consanguineous Turkish family. Although the relationship between the various genotypes and phenotypes in Krabbe disease has not been fully elucidated an accurate genetic family study is helpful for genetic counseling follow-up and therapy of Krabbe disease. Also, it is important to identify new mutations in order to clarify their clinical importance, to assess the prognosis of the disease, and to suggest either prenatal diagnosis or preimplantation genetic diagnosis to the effected families.