A Novel Mutation in an Iranian Patient Affected by Cystinosis: A Case Report and Literature Review

Abstract

Background: Cystinosis is a rare lysosomal storage disorder with autosomal recessive inheritance caused by mutations in the CTNS gene, which leads to the accumulation of cystine crystals in lysosomes and gradual damage to various tissues and organs in the body. In this study, we investigated the variants in the CTNS gene of two cystinosis patients who were referred to Ali Asghar Children's Hospital. Additionally, we review previouse reports of pathogenic/likely pathogenic variants in the CTNS gene in Iran and some Middle Eastern countries, including Saudi Arabia, Turkey, and Egypt.

Methods: After collecting clinical and paraclinical data, sequencing of all exons of the CTNS gene along with its boundary regions was performed. To interpret the identified variants, bioinformatics tools based on the ACMG guideline were used.

Results: In the first patient, a novel variant c.1055A>G was found in the homozygous state, which, based on bioinformatics criteria, was classified as a "likely pathogenic" variant. In the second patient, a known homozygous of c.1015G>A was identified in the which has been previously reported as a pathogenic variant.

Conclusion: The results of this study introduce a new variant in the CTNS gene. Furthermore, by comparing reported variants in countries from the Middle East, including Iran, Saudi Arabia, Turkey, and Egypt, the c.681G>A variant was identified as the most common variant in Iran, Turkey, and Saudi Arabia, while the c.829dup variant was the most common in Egypt. The findings highlight the importance of genetic testing for definitive diagnosis and the need for targeted screening strategies in populations with high rates of consanguineous marriage