First Report of <i>CTNS</i> Mutations in a Chinese Family with Infantile Cystinosis

Yang, Yongjia; Hu, Yuan; Zhao, Rui; He, Xinyu; Zhao, Lingxia; Tu, Min; Zhou, Lijun; Guo, Jihong; Long, Wenyong; Zhao, Tantai; Zhu, Yimin

doi:10.1155/2015/309410

Cited by 5 publications

(6 citation statements)

References 18 publications

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“…Cystinosis is also reported in countries with high levels of consanguinity such as some countries in the Middle East, but accurate prevalence data are lacking 58,61–64 . The low reported frequency of cystinosis in Russia 65 , India 66 and China 67 likely reflects underdiagnosis.…”

Section: Cystinosis: An Overviewmentioning

confidence: 99%

The renal Fanconi syndrome in cystinosis: pathogenic insights and therapeutic perspectives

2016

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Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders. It is caused by a defect in the lysosomal cystine transporter, cystinosin, which results in an accumulation of cystine in all organs. Despite the ubiquitous expression of cystinosin, a renal Fanconi syndrome is often the first manifestation of cystinosis, usually presenting within the first year of life and characterized by the early and severe dysfunction of proximal tubule cells, highlighting the unique vulnerability of this cell type. The current therapy for cystinosis, cysteamine, facilitates lysosomal cystine clearance and greatly delays progression to kidney failure but is unable to correct the Fanconi syndrome. This Review summarizes decades of studies that have fostered a better understanding of the pathogenesis of the renal Fanconi syndrome associated with cystinosis. These studies have unraveled some of the early molecular changes that occur before the onset of tubular atrophy and identified a role for cystinosin beyond cystine transport, in endolysosomal trafficking and proteolysis, lysosomal clearance, autophagy and the regulation of energy balance. These studies have also led to the identification of new potential therapeutic targets and here, we outline the potential role of stem cell therapy for cystinosis and provide insights into the mechanism of haematopoietic stem cell-mediated kidney protection.

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Section: Cystinosis: An Overviewmentioning

confidence: 99%

The renal Fanconi syndrome in cystinosis: pathogenic insights and therapeutic perspectives

2016

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“…Interestingly, c.681G>A (p.Glu227 * ) is the overall most frequently identified allele detected in all Middle eastern cohorts and most variant represent stop or frameshift alleles (Table 1) (17–22, 26). Studies investigating CTNS mutations in Cystinosis patients from the Far East have likewise reported several alleles including compound heterozygous mutation c.329G>C, c.329+2T>C in Japan, c.926G>A, c.850C>T, c.18-21del/c and c.969C>G in Thailand, and compound heterozygous mutations c.329+1del andc.463_464del in China while none of the reported cases carried the 57-kb deletion (27–29) but a smaller deletion encompassing ~20 kb of genomic DNA extending from CARKL intron 1 to CTNS intron 6, c.771–793del, and a c.1515G>A variant have been reported in Tunisian nephrotic patients (30). The 57-kb deletion has however been previously detected in patients from African American ethnicity (31).…”

Section: Discussionmentioning

confidence: 99%

A 57 kB Genomic Deletion Causing CTNS Loss of Function Contributes to the CTNS Mutational Spectrum in the Middle East

et al. 2019

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Background: Nephropathic Cystinosis, the most common cause of renal Fanconi syndrome, is a lysosomal transport disorder with an autosomal recessive inheritance pattern. A large number of mutations in CTNS have been identified as causative to date. A 57 kb deletion encompassing parts of CTNS is most commonly identified in Caucasians but this allele has not been identified in individuals of Eastern Mediterranean, Middle Eastern, Persian, or Arab origin to date. Methods and Results: Implementing whole exome sequencing (WES) in a consanguineous Iranian family, we identified this large deletion affecting CTNS in a patient initially presenting with hypokalemic metabolic alkalosis symptoms and considerable proteinuria. Conclusion: We show WES is a cost and time efficient genetic diagnostics modality to identify the underlying molecular pathology in Cystinosis individuals and provide a summary of all previously reported CTNS alleles in the Middle east population. Our work also highlights the importance to consider the 57-kb deletion as underlying genetic cause in non-European populations, including the Middle East. Limited diagnostic modalities for Cystinosis in developing countries could account for the lack of previously reported cases in these populations carrying this allele. Further, our findings emphasize the utility of WES to define genetic causes in clinically poorly defined phenotypes and demonstrate the requirement of Copy number variation (CNV) analysis of WES data.

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“…Up to date, most of the reported cases of cystinosis have occurred in Europe and the United States, with much less cases of cystinosis reported in Asia. Specifically, one case in Japan (7), 6 cases in Thailand (4 families involved) (8), 2 cases in India (9), and 21 cases in China have been reported (Table 1) (3,5,6,(10)(11)(12)(13). The Chinese cases included 10 Mainland families (including 13 patients with CTNS homozygous mistranslation variant N323K, c.681 G > A(p.E227E), c.477C > G (p.S159R), c.274C > T (p.Q92X), c.680A > T (p.E227V) and CTNS pathogenic variant of (IVS6+1, del G and IVS8-1, and del GT), or with a deletion of c.18_21del GACT, (p.T7FfsX7)), and 5 Taiwanese families (including 8 patients with CTNS homozygous mistranslation variant N323K, 753G > A(W138X), exon 11 (IVS11+2T > C), 1178A-G (K280R) or mutation 57-kb deletion cystinosis).…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, some progress has been made in the study of the disease in developed countries. However, relatively few reviews or case reports from China have been published (3)(4)(5)(6). Furthermore, cases of cystinosis in children are particularly rare, which may be related to the low incidence of the disease and also the understanding of the disease.…”

Section: Introductionmentioning

confidence: 99%

Case Report: Cystinosis in a Chinese Child With a Novel CTNS Pathogenic Variant

et al. 2022

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ObjectiveTo report a rare case of cystinosis with a novel CTNS pathogenic variant in the Chinese population.MethodsRetrospective analysis of the clinical manifestations, laboratory results, and gene detection data of a child with cystinosis.ResultsA Chinese Zang ethnic girl could not stand or walk until 3 years old, with additional symptoms including a loss of appetite. Since then, the girl gradually exhibited “X” leg, double wrist joints, a bilateral ankle deformity, and rickets. At the age of 9 years, the girl was hospitalized. Laboratory testing showed that her blood phosphorus, blood calcium and blood potassium levels were significantly decreased. At the same time, the girl's urine glucose and urine protein were positive, although her fasting blood glucose, glycosylated hemoglobin, and 75 g glucose tolerance were not significantly abnormal. Further, blood gas analysis showed metabolic acidosis. These symptoms corresponded to Fanconi syndrome. Gene analysis showed that there was a homozygous pathogenic variant c.140 ≤ 5G > A (p.?) in the CTNS gene, which was a small variation in the intron region. To our knowledge, this is the first report of the rare variant.ConclusionAttention should be paid to the differential diagnosis of cystinosis by gene analysis in children whose clinical manifestations include exercise dysplasia, renal damage, or multiple organ damage (including bone, thyroid, etc) and who cannot be firmly diagnosed for the time being.

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First Report of CTNS Mutations in a Chinese Family with Infantile Cystinosis

Cited by 5 publications

References 18 publications

The renal Fanconi syndrome in cystinosis: pathogenic insights and therapeutic perspectives

The renal Fanconi syndrome in cystinosis: pathogenic insights and therapeutic perspectives

A 57 kB Genomic Deletion Causing CTNS Loss of Function Contributes to the CTNS Mutational Spectrum in the Middle East

Case Report: Cystinosis in a Chinese Child With a Novel CTNS Pathogenic Variant

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