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Cystinosis and two rare mutations in CTNS gene: two case reports
BACKGROUND: 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 Tra...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074344/ https://www.ncbi.nlm.nih.gov/pubmed/35513889 http://dx.doi.org/10.1186/s13256-022-03379-7 |
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author | Gholami Yarahmadi, Sepideh Sarlaki, Fatemeh Morovvati, Saeid |
author_facet | Gholami Yarahmadi, Sepideh Sarlaki, Fatemeh Morovvati, Saeid |
author_sort | Gholami Yarahmadi, Sepideh |
collection | PubMed |
description | BACKGROUND: 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 (CTNS), encodes the lysosomal cystine carrier cystinosin. CASE PRESENTATION: 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 CTNS 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 CTNS gene. At least 148 different pathogenic and deleterious mutations in the CTNS gene have been reported to date. Owing to our patient’s prominent clinical features of cystinosis, we carried out a targeted search for mutations in the CTNS gene. CONCLUSIONS: 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 CTNS 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. |
format | Online Article Text |
id | pubmed-9074344 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-90743442022-05-07 Cystinosis and two rare mutations in CTNS gene: two case reports Gholami Yarahmadi, Sepideh Sarlaki, Fatemeh Morovvati, Saeid J Med Case Rep Case Report BACKGROUND: 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 (CTNS), encodes the lysosomal cystine carrier cystinosin. CASE PRESENTATION: 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 CTNS 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 CTNS gene. At least 148 different pathogenic and deleterious mutations in the CTNS gene have been reported to date. Owing to our patient’s prominent clinical features of cystinosis, we carried out a targeted search for mutations in the CTNS gene. CONCLUSIONS: 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 CTNS 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. BioMed Central 2022-05-06 /pmc/articles/PMC9074344/ /pubmed/35513889 http://dx.doi.org/10.1186/s13256-022-03379-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Case Report Gholami Yarahmadi, Sepideh Sarlaki, Fatemeh Morovvati, Saeid Cystinosis and two rare mutations in CTNS gene: two case reports |
title | Cystinosis and two rare mutations in CTNS gene: two case reports |
title_full | Cystinosis and two rare mutations in CTNS gene: two case reports |
title_fullStr | Cystinosis and two rare mutations in CTNS gene: two case reports |
title_full_unstemmed | Cystinosis and two rare mutations in CTNS gene: two case reports |
title_short | Cystinosis and two rare mutations in CTNS gene: two case reports |
title_sort | cystinosis and two rare mutations in ctns gene: two case reports |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074344/ https://www.ncbi.nlm.nih.gov/pubmed/35513889 http://dx.doi.org/10.1186/s13256-022-03379-7 |
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