Clinical Characteristics and In Silico Analysis of Cystinuria Caused by a Novel <i>SLC3A1</i> Mutation
Cystinuria is a genetically inherited disorder of renal and intestinal transport, featured as a high concentration of cystine in the urine. Cumulative cystine in urine would cause the formation of kidney stones, which further leads to renal colic and dysfunction. Gene screens have found that mutatio...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Genes |
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| author | Lexin Liu Zihao Xu Yuelin Guan Ying Zhang Xue Li Yunqing Ren Lidan Hu Xiang Yan |
| author_facet | Lexin Liu Zihao Xu Yuelin Guan Ying Zhang Xue Li Yunqing Ren Lidan Hu Xiang Yan |
| author_sort | Lexin Liu |
| collection | DOAJ |
| description | Cystinuria is a genetically inherited disorder of renal and intestinal transport, featured as a high concentration of cystine in the urine. Cumulative cystine in urine would cause the formation of kidney stones, which further leads to renal colic and dysfunction. Gene screens have found that mutations in <i>SLC3A1 or SLC7A9</i> gene are responsible for most cases of cystinuria, for encoding defective cystine transporters. Here, we presented the genotypic and phenotypic characteristics of one unique case of a three-generation Chinese family. The proband developed severe urolithiasis combined with renal damage. The radiography and computed tomography (CT) scan showed calculus in the left pelvic kidney. Postoperative stone analysis revealed that the stones were mainly composed of cystine. Therefore, to explore its pathogenesis, next-generation Whole Exome Sequencing (WES) and Sanger sequencing identify the proband mutated gene of the proband’s family. In this article, we reported novel compound heterozygous mutations (c.818G>A and c.1011G>A) of the <i>SLC3A1</i> gene in a 5-year-old child suffering from a cystine stone from a three-generation family. Bioinformatic analysis was used to predict the pathogenicity and conservation of the target mutation. Conservative sequence and evolutionary conservation analysis indicated that cystine<sup>273</sup> and proline<sup>337</sup> were highly conserved among species, and both mutations listed here (Cys273Tyr and Pro337Pro) were pathogenic. To conclude, our study expands the phenotypic and genotypic spectrum of <i>SLC3A1</i> and indicates that genetic screening should be considered in the clinic to provide more effective and precise treatment for cystinuria. |
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| last_indexed | 2024-03-09T18:18:19Z |
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| spelling | doaj.art-1af2bd54969d4eaa8bdb6f10edc757d52023-11-24T08:27:26ZengMDPI AGGenes2073-44252022-11-011311217310.3390/genes13112173Clinical Characteristics and In Silico Analysis of Cystinuria Caused by a Novel <i>SLC3A1</i> MutationLexin Liu0Zihao Xu1Yuelin Guan2Ying Zhang3Xue Li4Yunqing Ren5Lidan Hu6Xiang Yan7Department of Urology, Pediatric Urolith Center, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, ChinaDepartment of Urology, Pediatric Urolith Center, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, ChinaThe Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, ChinaInstitute of Translational Medicine, Zhejiang University School of Medicine, 268 Kaixuan Road, Hangzhou 310029, ChinaDepartment of Big Data in Health Science School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Dermatology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, ChinaThe Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, ChinaDepartment of Urology, Pediatric Urolith Center, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, ChinaCystinuria is a genetically inherited disorder of renal and intestinal transport, featured as a high concentration of cystine in the urine. Cumulative cystine in urine would cause the formation of kidney stones, which further leads to renal colic and dysfunction. Gene screens have found that mutations in <i>SLC3A1 or SLC7A9</i> gene are responsible for most cases of cystinuria, for encoding defective cystine transporters. Here, we presented the genotypic and phenotypic characteristics of one unique case of a three-generation Chinese family. The proband developed severe urolithiasis combined with renal damage. The radiography and computed tomography (CT) scan showed calculus in the left pelvic kidney. Postoperative stone analysis revealed that the stones were mainly composed of cystine. Therefore, to explore its pathogenesis, next-generation Whole Exome Sequencing (WES) and Sanger sequencing identify the proband mutated gene of the proband’s family. In this article, we reported novel compound heterozygous mutations (c.818G>A and c.1011G>A) of the <i>SLC3A1</i> gene in a 5-year-old child suffering from a cystine stone from a three-generation family. Bioinformatic analysis was used to predict the pathogenicity and conservation of the target mutation. Conservative sequence and evolutionary conservation analysis indicated that cystine<sup>273</sup> and proline<sup>337</sup> were highly conserved among species, and both mutations listed here (Cys273Tyr and Pro337Pro) were pathogenic. To conclude, our study expands the phenotypic and genotypic spectrum of <i>SLC3A1</i> and indicates that genetic screening should be considered in the clinic to provide more effective and precise treatment for cystinuria.https://www.mdpi.com/2073-4425/13/11/2173<i>SLC3A1</i>cystinuriacystine stonegenetic mutationwhole exome sequencing |
| spellingShingle | Lexin Liu Zihao Xu Yuelin Guan Ying Zhang Xue Li Yunqing Ren Lidan Hu Xiang Yan Clinical Characteristics and In Silico Analysis of Cystinuria Caused by a Novel <i>SLC3A1</i> Mutation Genes <i>SLC3A1</i> cystinuria cystine stone genetic mutation whole exome sequencing |
| title | Clinical Characteristics and In Silico Analysis of Cystinuria Caused by a Novel <i>SLC3A1</i> Mutation |
| title_full | Clinical Characteristics and In Silico Analysis of Cystinuria Caused by a Novel <i>SLC3A1</i> Mutation |
| title_fullStr | Clinical Characteristics and In Silico Analysis of Cystinuria Caused by a Novel <i>SLC3A1</i> Mutation |
| title_full_unstemmed | Clinical Characteristics and In Silico Analysis of Cystinuria Caused by a Novel <i>SLC3A1</i> Mutation |
| title_short | Clinical Characteristics and In Silico Analysis of Cystinuria Caused by a Novel <i>SLC3A1</i> Mutation |
| title_sort | clinical characteristics and in silico analysis of cystinuria caused by a novel i slc3a1 i mutation |
| topic | <i>SLC3A1</i> cystinuria cystine stone genetic mutation whole exome sequencing |
| url | https://www.mdpi.com/2073-4425/13/11/2173 |
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