Bayrakli Fatih, Poyrazoglu Hatice Gamze, Yuksel Sirin, Yakicier Cengiz, Erguner Bekir, Sagiroglu Mahmut Samil, Yuceturk Betul, Ozer Bugra, Doganay Selim, Tanrikulu Bahattin, Seker Askin, Akbulut Fatih, Ozen Ali, Per Huseyin, Kumandas Sefer, Altuner Torun Yasemin, Bayri Yasar, Sakar Mustafa, Dagcinar Adnan, Ziyal Ibrahim
Department of Neurosurgery, Marmara University School of Medicine, Istanbul, Turkey.
Institute of Neurological Sciences, Marmara University, Istanbul, Turkey.
J Hum Genet. 2015 Dec;60(12):763-8. doi: 10.1038/jhg.2015.109. Epub 2015 Oct 1.
We report an association between a new causative gene and spastic paraplegia, which is a genetically heterogeneous disorder. Clinical phenotyping of one consanguineous family followed by combined homozygosity mapping and whole-exome sequencing analysis. Three patients from the same family shared common features of progressive complicated spastic paraplegia. They shared a single homozygous stretch area on chromosome 6. Whole-exome sequencing revealed a homozygous mutation (c.853_871del19) in the gene coding the kinesin light chain 4 protein (KLC4). Meanwhile, the unaffected parents and two siblings were heterozygous and one sibling was homozygous wild type. The 19 bp deletion in exon 6 generates a stop codon and thus a truncated messenger RNA and protein. The association of a KLC4 mutation with spastic paraplegia identifies a new locus for the disease.
我们报告了一个新的致病基因与痉挛性截瘫之间的关联，痉挛性截瘫是一种具有遗传异质性的疾病。对一个近亲家庭进行临床表型分析，随后进行联合纯合性定位和全外显子组测序分析。来自同一家庭的三名患者具有进行性复杂性痉挛性截瘫的共同特征。他们在6号染色体上共享一个单一的纯合延伸区域。全外显子组测序揭示了编码驱动蛋白轻链4蛋白（KLC4）的基因中存在一个纯合突变（c.853_871del19）。同时，未受影响的父母和两个兄弟姐妹为杂合子，一个兄弟姐妹为纯合野生型。外显子6中的19bp缺失产生一个终止密码子，从而产生截短的信使RNA和蛋白质。KLC4突变与痉挛性截瘫的关联确定了该疾病的一个新位点。
