Department of Advanced Sciences and Technology, Islamic Azad University-Tehran Medical Sciences, Zargandeh, Shariati, Tehran, Iran.
Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Med Case Rep. 2022 May 6;16(1):181. doi: 10.1186/s13256-022-03379-7.
Cystinosis is an autosomal recessive disorder characterized by an accumulation of the amino acid cystine in lysosomes throughout the body. Cystinosis is an inherited disease resulting from the failure of lysosomal cystine transport. The responsible gene, Cystinosin, Lysosomal Cystine Transporter (CTNS), encodes the lysosomal cystine carrier cystinosin.
In this case report, we reviewed the genetic basis of cystinosis and investigated two Iranian cases affected by cystinosis, one of which revealed a rare mutation in the CTNS gene. Two patients, 9-year-old (patient A) and 11-year-old (patient B) symptomatic Iranian females with renal insufficiency, were diagnosed with cystinosis on the basis of their clinical features and laboratory tests. After genetic counseling, blood samples were obtained from the patients and their parents. Genomic Deoxyribonucleic Acid (DNA) was extracted from whole blood, and mutation analysis was performed using polymerase chain reaction and sequencing methods for all exons of the CTNS gene. At least 148 different pathogenic and deleterious mutations in the CTNS gene have been reported to date. Owing to our patient's prominent clinical features of cystinosis, we carried out a targeted search for mutations in the CTNS gene.
This led us to confirm the existence of a homozygous DNA variation c.257_258deletionCT (p.Ser86PhefsTer38) in exon 6 of the gene in patient A and another homozygous DNA variation, c.323delA (p.Q108RfsTer10), in the same exon in patient B. As expected, the mentioned mutation existed in both her parents in a heterozygous state. Variations c.257_258delCT and c.323delA reported in three Iranian patients in the CTNS gene are frameshifts, and truncating mutations that affect product function result in relatively mild symptoms of cystinosis. The present finding confirms previous research and proves the importance of the association of this gene rare mutations with cystinosis. Since reported mutations are rare, their previous reports in Iranian patients indicate the high frequency of these mutations in our region.
胱氨酸贮积症是一种常染色体隐性遗传病，其特征是全身溶酶体中胱氨酸的积累。胱氨酸贮积症是一种遗传性疾病，是由于溶酶体胱氨酸转运的失败导致的。负责该疾病的基因，胱氨酸转运蛋白（CTNS），编码溶酶体胱氨酸载体胱氨酸。
在本病例报告中，我们回顾了胱氨酸贮积症的遗传基础，并研究了两名受胱氨酸贮积症影响的伊朗患者，其中一名患者 CTNS 基因中存在罕见突变。两名患者，9 岁（患者 A）和 11 岁（患者 B）的伊朗女性，均有肾功能不全的症状，根据其临床特征和实验室检查结果诊断为胱氨酸贮积症。在进行遗传咨询后，从患者及其父母处采集血样。从全血中提取基因组脱氧核糖核酸（DNA），并使用聚合酶链反应和测序方法对 CTNS 基因的所有外显子进行突变分析。迄今为止，已经报道了至少 148 种不同的致病性和有害性 CTNS 基因突变。由于我们患者胱氨酸贮积症的显著临床特征，我们对 CTNS 基因中的突变进行了有针对性的搜索。
这导致我们在患者 A 的基因外显子 6 中确认存在纯合 DNA 变异 c.257_258deletionCT（p.Ser86PhefsTer38），在患者 B 的同一外显子中存在另一种纯合 DNA 变异 c.323delA（p.Q108RfsTer10）。正如预期的那样，所述突变在她的父母中均以杂合状态存在。在 CTNS 基因中报道的三位伊朗患者的变异 c.257_258delCT 和 c.323delA 是移码突变，截断突变会影响产物功能，导致胱氨酸贮积症的症状相对较轻。本研究结果证实了先前的研究，并证明了该基因罕见突变与胱氨酸贮积症之间的关联非常重要。由于报道的突变是罕见的，它们在伊朗患者中的先前报道表明，这些突变在我们的地区非常常见。
