Jaradat Saied, Al-Rababah Bothina, Hazza Issa, Akl Kamal, Saca Edward, Al-Younis Doaa
Princess Haya Biotechnology Center, Jordan University of Science and Technology, Irbid, Jordan.
Princess Haya Biotechnology Center, Jordan University of Science and Technology, Irbid, Jordan.
Nefrologia. 2015 Nov-Dec;35(6):547-53. doi: 10.1016/j.nefro.2015.09.009. Epub 2015 Nov 10.
Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder that is characterised by the accumulation of the amino acid cystine in several body tissues due to a mutation in the CTNS gene, which encodes the cystinosin protein. The aim of this study was to sequence the coding exons of the CTNS gene in five different Jordanian families and one family from Sudan with nephropathic cystinosis.
Probands initially presented with Fanconi syndrome symptoms. An eye examination showed the accumulation of cystine crystals in the cornea by the age of 2 years, suggesting cystinosis. All of the coding exons and flanking intronic sequences and the promoter region of the CTNS gene were amplified using polymerase chain reaction and subjected to sequencing.
None of the probands in this study carried the European 57-kb deletion in the CTNS gene. Seven variants in the coding and promoter sequence of the CTNS gene were identified in the probands of this study. Two of these variants were a CTNS mutation that was previously identified in a heterozygous genotype in two different patients of European descendant. The two mutations were c.829dupA in exon 10 and c.890G>A in exon 11. The proband of family 2 was compound-heterozygous for the two mutations.
This study is the first molecular study of infantile nephropathic cystinosis in Jordan. We successfully identified the causative CTNS mutations in Jordanian families. The results provide a basis for the early detection of the disease using molecular tools in a highly consanguineous Jordanian population.
肾病型胱氨酸贮积症是一种常染色体隐性溶酶体贮积病，其特征是由于编码胱氨酸转运蛋白的CTNS基因突变，导致氨基酸胱氨酸在多个身体组织中蓄积。本研究的目的是对五个不同的约旦家庭以及一个来自苏丹的患有肾病型胱氨酸贮积症的家庭中的CTNS基因编码外显子进行测序。
先证者最初表现出范科尼综合征症状。眼科检查显示，到2岁时角膜中有胱氨酸结晶蓄积，提示为胱氨酸贮积症。使用聚合酶链反应扩增CTNS基因的所有编码外显子、侧翼内含子序列和启动子区域，并进行测序。
本研究中的先证者均未携带CTNS基因的欧洲57 kb缺失。在本研究的先证者中鉴定出CTNS基因编码和启动子序列中的7个变异。其中两个变异是CTNS突变，先前在两名不同欧洲后裔患者中以杂合基因型被鉴定出来。这两个突变分别是外显子10中的c.829dupA和外显子11中的c.890G>A。2号家庭的先证者这两个突变呈复合杂合状态。
本研究是约旦关于婴儿肾病型胱氨酸贮积症的首次分子研究。我们成功鉴定出约旦家庭中导致该病的CTNS突变。研究结果为在高度近亲通婚的约旦人群中使用分子工具早期检测该疾病提供了依据。
