A 57 kB genomic deletion causing CTNS loss of function contributes to the CTNS mutational spectrum in the middle east

Najafi, M. and Tamandani, D. M. K. and Azarfar, A. and Bakey, Z. and Behjati, F. and Antony, D. and Schüle, I. and Sadeghi-Bojd, S. and Karimiani, E. G. and Schmidts, M. (2019) A 57 kB genomic deletion causing CTNS loss of function contributes to the CTNS mutational spectrum in the middle east. Frontiers in Pediatrics, 7 (MAR).

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Abstract

Background: Nephropathic Cystinosis, the most common cause of renal Fanconi syndrome, is a lysosomal transport disorder with an autosomal recessive inheritance pattern. A large number of mutations in CTNS have been identified as causative to date. A 57 kb deletion encompassing parts of CTNS is most commonly identified in Caucasians but this allele has not been identified in individuals of Eastern Mediterranean, Middle Eastern, Persian, or Arab origin to date. Methods and Results: Implementing whole exome sequencing (WES) in a consanguineous Iranian family, we identified this large deletion affecting CTNS in a patient initially presenting with hypokalemic metabolic alkalosis symptoms and considerable proteinuria. Conclusion: We show WES is a cost and time efficient genetic diagnostics modality to identify the underlying molecular pathology in Cystinosis individuals and provide a summary of all previously reported CTNS alleles in the Middle east population. Our work also highlights the importance to consider the 57-kb deletion as underlying genetic cause in non-European populations, including the Middle East. Limited diagnostic modalities for Cystinosis in developing countries could account for the lack of previously reported cases in these populations carrying this allele. Further, our findings emphasize the utility of WES to define genetic causes in clinically poorly defined phenotypes and demonstrate the requirement of Copy number variation (CNV) analysis of WES data. © 2019 Najafi, Tamandani, Azarfar, Bakey, Behjati, Antony, Schüle, Sadeghi-Bojd, Karimiani and Schmidts.

Item Type: Article
Additional Information: Export Date: 16 February 2020 Correspondence Address: Tamandani, D.M.K.; Department of Biology, University of Sistan and BaluchestanIran; email: dorkordi@yahoo.com
Uncontrolled Keywords: CTNS deletion Cystinosis Iran Middle East population Tubulopathy genomic DNA Article autosomal recessive inheritance birth weight case report child clinical article consanguinity disease severity end stage renal disease gene deletion gene mutation genetic counseling human Iranian people kidney graft rejection male Middle East molecular diagnosis preschool child Sanger sequencing urinalysis venous blood whole exome sequencing
Subjects: WS Pediatrics
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib1 lib1
Date Deposited: 21 Jun 2020 09:26
Last Modified: 21 Jun 2020 09:26
URI: http://eprints.mums.ac.ir/id/eprint/18559

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