Genetic and clinical analysis of Chinese pediatric patients with cystinuria

Zhan, Ruichao; Ge, Yang; Liu, Yukun; Zhao, Zhenqiang; Wang, Wenying

doi:10.1007/s00240-022-01398-z

Cited by 2 publications

(2 citation statements)

References 21 publications

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“…For example, p.T216M in SLC3A1 and p.G105R in SLC7A9 are common in Greece and dupE5E9 is more commonly found in Germany. In the Asian population, SLC7A9 c.1445C>T (p.P482L) is common and might indicate a mutation hotspot in the Japanese population [6,27,28]. Among the total of 24 identified mutations, the aforementioned common mutations p.T216M and p.P482L were also found.…”

Section: Discussionmentioning

confidence: 99%

“…Although cystinuria is the most commonly inherited form of kidney stone disease, only 1% of all kidney stone disease cases are due to this disorder. Cystine stones account for 1-2% of urolithiasis in adults but 10% in children, and there are ethnic differences in worldwide prevalence [5,6]. Global prevalence is estimated to be 1 in 7000, and this value ranges from 1 in 100,000 (Swedish) to 1 in 2500 (Libyan).…”

Section: Introductionmentioning

confidence: 99%

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Clinical Course and Mutational Analysis of Patients with Cystine Stone: A Single-Center Experience

Jeong,

Oh,

Sohn

et al. 2023

Biomedicines

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Cystinuria is a known genetic disorder. To date, two genes, SLC3A1 and SLC7A9, have been identified as causes of cystinuria. In this study of 10 patients with cystinuria, which is the largest Korean cohort ever studied, we examined the patients’ phenotypes, clinical courses, and genetic analyses. A total of 10 patients with cystinuria diagnosed with cystine stones in a single tertiary medical center (Severance Hospital, Seoul, Republic of Korea) from April 2000 to July 2023 were included in the study. All of the patients participated in mutational studies, and the clinical presentation and consecutive laboratory findings of the patients were analyzed retrospectively. After the initial stone-related surgery or procedure at our hospital, 6 of the 10 patients underwent additional surgery at least once for recurrent stones. Genetic analyses identified six new mutations, of which only two patients had type B mutations. The most common genotype was compound heterozygous type A. We investigated the genotypes and clinical courses of 10 Korean patients with cystinuria who had not been previously reported. More data are needed to statistically analyze the genotype and phenotype of cystinuria.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical Course and Mutational Analysis of Patients with Cystine Stone: A Single-Center Experience

Jeong,

Oh,

Sohn

et al. 2023

Biomedicines

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Interpretation of SLC3A1 and SLC7A9 variants in cystinuria patients: The significance of the PM3 criterion and protein stability

Lee

Han

et al. 2023

Urolithiasis

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Cystinuria is a genetic disorder caused by defects in the b0,+ transporter system, which is composed of rBAT and b0,+AT coded by SLC3A1 and SLC7A9, respectively. Variants in SLC3A1 and SLC7A9 follow autosomal recessive inheritance and autosomal dominant inheritance with reduced penetrance, respectively, which complicates the interpretation of cystinuria-related variants. Here, we report seven different SLC3A1 variants and six different SLC7A9 variants. Among these variants were two novel variants previously not reported: SLC3A1 c.223C > T and SLC7A9 c.404A > G. In silico analysis using REVEL correlated well with the functional loss upon SLC7A9 variants with scores of 0.8560–0.9200 and 0.4970–0.5239 for severe and mild decrease in transport activity, respectively. In addition, DynaMut2 was able to predict a decreased protein expression level resulting from the SLC7A9 variant c.313G > A with a ΔΔGStability −2.93 kcal/mol. Our study adds to the literature as additional cases of a variant allow applying the PM3 criterion with higher strength level. In addition, we suggest the clinical utility of REVEL and DynaMut2 in interpreting SLC3A1 and SLC7A9 variants. While a decreased protein expression level is not embraced in the current variant interpretation guidelines, we believe in silico protein stability predicting tools could serve as evidence of protein function loss.

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Genetic and clinical analysis of Chinese pediatric patients with cystinuria

Cited by 2 publications

References 21 publications

Clinical Course and Mutational Analysis of Patients with Cystine Stone: A Single-Center Experience

Clinical Course and Mutational Analysis of Patients with Cystine Stone: A Single-Center Experience

Interpretation of SLC3A1 and SLC7A9 variants in cystinuria patients: The significance of the PM3 criterion and protein stability

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