Li Xiao-Qiao, Wu Di, Liang Xue-Jun, Li Wen-Jing, Liu Min, Cao Bing-Yan, Su Chang, Meng Xi, Gong Chun-Xiu
Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
J Pediatr Endocrinol Metab. 2019 Apr 24;32(4):375-382. doi: 10.1515/jpem-2018-0263.
Background Cystinosis is a rare autosomal-recessive disorder caused by a defective transport of cystine across the lysosomal membrane. Previous studies have mapped cystinosis to the CTNS gene which is located on chromosome 17p13, and various CTNS mutations have been identified to correlate them with this disease. Methods We analyzed six patients from five unrelated families who were diagnosed with cystinosis in our hospital. We described the diagnostic procedures for all the patients and proposed alternative therapies for cystinosis patients instead of using cysteamine, an orphan drug which was commercially unavailable in China. Moreover, genetic analysis of all patients' samples was carried out to identify novel CTNS gene mutations. Results and conclusions The patients in this study were followed up from 1 to more than 10 years to monitor their growth and development, which indicated that the alternative therapies we used were helpful to ameliorate the complications of the cystinosis patients without cysteamine. Furthermore, by sequencing the patients' genome, we identified novel mutations in the CTNS gene including: c.477C > G (p.S159R), c.274C > T (p.Q92X) and c.680A > T (p.E227V); these mutations were only observed in cystinosis patients and had never been reported in any other populations, suggesting they might be specific to Chinese cystinosis patients.
胱氨酸病是一种罕见的常染色体隐性疾病，由胱氨酸跨溶酶体膜转运缺陷引起。先前的研究已将胱氨酸病定位到位于17号染色体p13上的CTNS基因，并且已鉴定出各种CTNS突变与该疾病相关。方法：我们分析了我院诊断为胱氨酸病的来自五个无亲缘关系家庭的六名患者。我们描述了所有患者的诊断程序，并为胱氨酸病患者提出了替代疗法，而不是使用在中国无法商业获得的孤儿药半胱胺。此外，对所有患者样本进行了基因分析，以鉴定新的CTNS基因突变。结果与结论：本研究中的患者随访了1至10多年，以监测他们的生长发育，这表明我们使用的替代疗法有助于改善无半胱胺的胱氨酸病患者的并发症。此外，通过对患者基因组进行测序，我们在CTNS基因中鉴定出了新的突变，包括：c.477C＞G（p.S159R）、c.274C＞T（p.Q92X）和c.680A＞T（p.E227V）；这些突变仅在胱氨酸病患者中观察到，在任何其他人群中均未报道，表明它们可能是中国胱氨酸病患者特有的。
