{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T15:40:31Z","timestamp":1780760431221,"version":"3.54.1"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Med Case Reports"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>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 (<jats:italic>CTNS<\/jats:italic>), encodes the lysosomal cystine carrier cystinosin.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>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 <jats:italic>CTNS<\/jats:italic> 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 <jats:italic>CTNS<\/jats:italic> gene. At least 148 different pathogenic and deleterious mutations in the <jats:italic>CTNS<\/jats:italic> gene have been reported to date. Owing to our patient\u2019s prominent clinical features of cystinosis, we carried out a targeted search for mutations in the <jats:italic>CTNS<\/jats:italic> gene.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>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 <jats:italic>CTNS<\/jats:italic> 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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13256-022-03379-7","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T23:04:06Z","timestamp":1651791846000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cystinosis and two rare mutations in CTNS gene: two\u00a0case reports"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2228-3892","authenticated-orcid":false,"given":"Sepideh","family":"Gholami Yarahmadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4698-0932","authenticated-orcid":false,"given":"Fatemeh","family":"Sarlaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8838-1044","authenticated-orcid":false,"given":"Saeid","family":"Morovvati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"issue":"4","key":"3379_CR1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1086\/302509","volume":"18","author":"M Town","year":"1998","unstructured":"Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, et\u00a0al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet. 1998;18(4):319\u201324. https:\/\/doi.org\/10.1086\/302509.","journal-title":"Nat Genet"},{"issue":"2","key":"3379_CR2","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1086\/302509","volume":"347","author":"WA Gahl","year":"2002","unstructured":"Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med. 2002;347(2):111\u201321. https:\/\/doi.org\/10.1086\/302509.","journal-title":"N Engl J Med"},{"issue":"11","key":"3379_CR3","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1086\/302509","volume":"17","author":"V Kalatzis","year":"2002","unstructured":"Kalatzis V, Antignac C. Cystinosis: from gene to disease. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Renal Assoc. 2002;17(11):1883\u20136. https:\/\/doi.org\/10.1086\/302509.","journal-title":"Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Renal Assoc."},{"issue":"3","key":"3379_CR4","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1086\/302509","volume":"18","author":"V Kalatzis","year":"2003","unstructured":"Kalatzis V, Antignac C. New aspects of the pathogenesis of cystinosis. Pediatr Nephrol. 2003;18(3):207\u201315. https:\/\/doi.org\/10.1086\/302509.","journal-title":"Pediatr Nephrol"},{"issue":"8","key":"3379_CR5","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.1086\/302509","volume":"13","author":"R Kleta","year":"2002","unstructured":"Kleta R, Gahl WA. Cystinosis: antibodies and healthy bodies. J Am Soc Nephrol. 2002;13(8):2189\u201391. https:\/\/doi.org\/10.1086\/302509.","journal-title":"J Am Soc Nephrol"},{"key":"3379_CR6","unstructured":"Nesterova G, Gahl WA. Cystinosis. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et\u00a0al., editors. GeneReviews. Seattle [WA] 1993."},{"issue":"2","key":"3379_CR7","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1101\/gr.10.2.165","volume":"10","author":"JW Touchman","year":"2000","unstructured":"Touchman JW, Anikster Y, Dietrich NL, Maduro VV, McDowell G, Shotelersuk V, et\u00a0al. The genomic region encompassing the nephropathic cystinosis gene [CTNS]: complete sequencing of a 200-kb segment and discovery of a novel gene within the common cystinosis-causing deletion. Genome Res. 2000;10(2):165\u201373.","journal-title":"Genome Res"},{"issue":"2","key":"3379_CR8","first-page":"187","volume":"74","author":"NK Devaraj","year":"2019","unstructured":"Devaraj NK, Aneesa AR, Abdul Hadi AM, Shaira N. Topical corticosteroids in clinical practice. Med J Malaysia. 2019;74(2):187\u20139.","journal-title":"Med J Malaysia"},{"key":"3379_CR9","doi-asserted-by":"crossref","unstructured":"Devaraj NK. A recurrent cutaneous eruption. BMJ Case Rep. 2019;12(2).","DOI":"10.1136\/bcr-2018-228355"},{"issue":"13","key":"3379_CR10","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1086\/302509","volume":"13","author":"V Kalatzis","year":"2004","unstructured":"Kalatzis V, Nevo N, Cherqui S, Gasnier B, Antignac C. Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin. Hum Mol Genet. 2004;13(13):1361\u201371. https:\/\/doi.org\/10.1086\/302509.","journal-title":"Hum Mol Genet"},{"issue":"6","key":"3379_CR11","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1086\/302509","volume":"14","author":"Y Anikster","year":"1999","unstructured":"Anikster Y, Shotelersuk V, Gahl WA. CTNS mutations in patients with cystinosis. Hum Mutat. 1999;14(6):454\u20138. https:\/\/doi.org\/10.1086\/302509.","journal-title":"Hum Mutat"},{"issue":"13","key":"3379_CR12","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.1086\/302509","volume":"8","author":"M Attard","year":"1999","unstructured":"Attard M, Jean G, Forestier L, Cherqui S, van\u2019t Hoff W, Broyer M, et\u00a0al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Human Mol Genet. 1999;8(13):2507\u201314. https:\/\/doi.org\/10.1086\/302509.","journal-title":"Human Mol Genet."},{"issue":"8","key":"3379_CR13","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1086\/302509","volume":"48","author":"KA Freed","year":"2011","unstructured":"Freed KA, Blangero J, Howard T, Johnson MP, Curran JE, Garcia YR, et\u00a0al. The 57 kb deletion in cystinosis patients extends into TRPV1 causing dysregulation of transcription in peripheral blood mononuclear cells. J Med Genet. 2011;48(8):563\u20136. https:\/\/doi.org\/10.1086\/302509.","journal-title":"J Med Genet"},{"issue":"5","key":"3379_CR14","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1086\/302509","volume":"63","author":"V Shotelersuk","year":"1998","unstructured":"Shotelersuk V, Larson D, Anikster Y, McDowell G, Lemons R, Bernardini I, et\u00a0al. CTNS mutations in an American-based population of cystinosis patients. Am J Hum Genet. 1998;63(5):1352\u201362. https:\/\/doi.org\/10.1086\/302509.","journal-title":"Am J Hum Genet"},{"issue":"2","key":"3379_CR15","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1086\/302509","volume":"65","author":"L Forestier","year":"1999","unstructured":"Forestier L, Jean G, Attard M, Cherqui S, Lewis C, van\u2019t Hoff W, et\u00a0al. Molecular characterization of CTNS deletions in nephropathic cystinosis: development of a PCR-based detection assay. Am J Human Genet. 1999;65(2):353\u20139. https:\/\/doi.org\/10.1086\/302509.","journal-title":"Am J Human Genet"},{"key":"3379_CR16","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/sj.ejhg.5200993","volume":"11","author":"SPG Mason","year":"2003","unstructured":"Mason SPG, Dall\u2019Amico R, Tartaglia S, Casciani S, Greco M, Bencivenga P, Murer L, Rizzoni G, Tenconi R, Clementi M. Mutational spectrum of the CTNS gene in Italy. Eur J Hum Genet. 2003;11:503\u20138. https:\/\/doi.org\/10.1038\/sj.ejhg.5200993.","journal-title":"Eur J Hum Genet"},{"issue":"2","key":"3379_CR17","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.gene.2012.03.047","volume":"499","author":"P Yeetong","year":"2012","unstructured":"Yeetong P, Tongkobpetch S, Kingwatanakul P, Deekajorndech T, Bernardini IM, Suphapeetiporn K, et\u00a0al. Two novel CTNS mutations in cystinosis patients in Thailand. Gene. 2012;499(2):323\u20135. https:\/\/doi.org\/10.1016\/j.gene.2012.03.047.","journal-title":"Gene"},{"issue":"3","key":"3379_CR18","doi-asserted-by":"publisher","first-page":"308","DOI":"10.3265\/Nefrologia.pre2012.Sep.11558","volume":"33","author":"S Shahkarami","year":"2013","unstructured":"Shahkarami S, Galehdari H, Ahmadzadeh A, Babaahmadi M, Pedram M. The first molecular genetics analysis of individuals suffering from nephropathic cystinosis in Southwestern Iran. Nefrol Publ Off Soc Espan Nefrol. 2013;33(3):308\u201315. https:\/\/doi.org\/10.3265\/Nefrologia.pre2012.Sep.11558.","journal-title":"Nefrol Publ Off Soc Espan Nefrol."},{"issue":"1","key":"3379_CR19","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s00467-011-1942-6","volume":"27","author":"R Topaloglu","year":"2012","unstructured":"Topaloglu R, Vilboux T, Coskun T, Ozaltin F, Tinloy B, Gunay-Aygun M, et\u00a0al. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr Nephrol. 2012;27(1):115\u201321. https:\/\/doi.org\/10.1007\/s00467-011-1942-6.","journal-title":"Pediatr Nephrol"},{"key":"3379_CR20","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/8904_2013_288","volume":"14","author":"NA Soliman","year":"2014","unstructured":"Soliman NA, Elmonem MA, van den Heuvel L, Abdel Hamid RH, Gamal M, Bongaers I, et\u00a0al. Mutational spectrum of the CTNS gene in Egyptian patients with nephropathic cystinosis. JIMD Rep. 2014;14:87\u201397. https:\/\/doi.org\/10.1007\/8904_2013_288.","journal-title":"JIMD Rep."},{"issue":"4","key":"3379_CR21","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3109\/13816810903200953","volume":"30","author":"MA Aldahmesh","year":"2009","unstructured":"Aldahmesh MA, Humeidan A, Almojalli HA, Khan AO, Rajab M, Abbas AL-A, et\u00a0al. Characterization of CTNS mutations in Arab patients with cystinosis. Ophthal Genet. 2009;30(4):185\u20139. https:\/\/doi.org\/10.3109\/13816810903200953.","journal-title":"Ophthal Genet."},{"issue":"3","key":"3379_CR22","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1089\/gte.2008.0014","volume":"12","author":"MA Alcantara-Ortigoza","year":"2008","unstructured":"Alcantara-Ortigoza MA, Belmont-Martinez L, Vela-Amieva M, Gonzalez-Del AA. Analysis of the CTNS gene in nephropathic cystinosis Mexican patients: report of four novel mutations and identification of a false positive 57-kb deletion genotype with LDM-2\/exon 4 multiplex PCR assay. Genet Test. 2008;12(3):409\u201314. https:\/\/doi.org\/10.1089\/gte.2008.0014.","journal-title":"Genet Test"},{"issue":"3","key":"3379_CR23","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.nefroe.2017.02.007","volume":"37","author":"F Ghazi","year":"2017","unstructured":"Ghazi F, Hosseini R, Akouchekian M, Teimourian S, Kachoei ZA, Otukesh H, Gahl WA, Behnam B. CTNS molecular genetics profile in a Persian nephropathic cystinosis population. Nefrolog\u00eda [English Edition]. 2017;37(3):301\u201310.","journal-title":"Nefrolog\u00eda [English Edition]."},{"issue":"1","key":"3379_CR24","first-page":"61","volume":"12","author":"F Bastug","year":"2018","unstructured":"Bastug F, Nalcacioglu H, Ozaltin F, Korkmaz E, Yel S. Nephropathic cystinosis mimicking Bartter syndrome: a novel mutation. Iran J Kidney Dis. 2018;12(1):61.","journal-title":"Iran J Kidney Dis"}],"container-title":["Journal of Medical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13256-022-03379-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13256-022-03379-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13256-022-03379-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T23:04:53Z","timestamp":1651791893000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmedicalcasereports.biomedcentral.com\/articles\/10.1186\/s13256-022-03379-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,6]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["3379"],"URL":"https:\/\/doi.org\/10.1186\/s13256-022-03379-7","relation":{},"ISSN":["1752-1947"],"issn-type":[{"value":"1752-1947","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,6]]},"assertion":[{"value":"22 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written consent for participating in this study was obtained from the parents of both patients. The study was performed in accordance with the principles of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patients for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors have no conflicts of interest to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"181"}}