Heil S G, Levtchenko E, Monnens L A, Trijbels F J, Van der Put N M, Blom H J
Department of Paediatrics, UMC St. Radboud, NL-6500 HB Nijmegen, The Netherlands.
Nephron. 2001 Sep;89(1):50-5. doi: 10.1159/000046043.
Infantile nephropathic cystinosis, an inborn error of metabolism with an autosomal recessive inheritance pattern, is characterized by lysosomal storage of the amino acid cystine due to an impaired transport of cystine out of the lysosomes. Initial clinical features consist of the renal Fanconi syndrome and crystals in the cornea. Oral therapy with cysteamine lowers the intracellular cystine content. Recently, the gene coding for the integral membrane protein cystinosin, which is responsible for membrane transport of cystine (CTNS), was cloned. Mutation analysis of the CTNS gene of Caucasian patients revealed a common 57-kb deletion, and several other mutations spread throughout the entire gene. In the present study, we developed an improved screening method for the detection of the common 57-kb deletion. By use of this method we detected the 57-kb deletion in 59% of the examined Dutch alleles. The remaining alleles were screened for other mutations by genomic sequencing of the different exons, revealing three previously described mutations. Furthermore, we studied a possible genotype-phenotype relation of the homozygous deleted patients, which could not be demonstrated in our study population. Next to biochemical determination of cystine in leukocytes or fibroblasts, molecular genetic analysis enables prenatal diagnosis and facilitates identification of carriers.
婴儿型肾病性胱氨酸病是一种常染色体隐性遗传模式的先天性代谢缺陷病，其特征是由于胱氨酸从溶酶体的转运受损，导致氨基酸胱氨酸在溶酶体中蓄积。最初的临床特征包括肾性范科尼综合征和角膜晶体。用半胱胺进行口服治疗可降低细胞内胱氨酸含量。最近，编码负责胱氨酸膜转运的整合膜蛋白胱氨酸转运体（CTNS）的基因被克隆。对白种人患者的CTNS基因进行突变分析发现了一个常见的57kb缺失，以及分布在整个基因中的其他几个突变。在本研究中，我们开发了一种改进的筛查方法来检测常见的57kb缺失。通过使用这种方法，我们在59%的检测荷兰等位基因中检测到了57kb缺失。其余等位基因通过对不同外显子进行基因组测序来筛查其他突变，发现了三个先前描述的突变。此外，我们研究了纯合缺失患者可能的基因型-表型关系，但在我们的研究人群中未能证实这种关系。除了对白细胞或成纤维细胞中的胱氨酸进行生化测定外，分子遗传学分析还能进行产前诊断并有助于携带者的鉴定。
