Identification of a Novel Non-Stop Mutation in PDE6C Gene in an Iranian Family With Con-Rod Dystrophy

  • Shahram Nasiri Department of Pediatric Neurology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  • Farah Talebi Milad Genetic Counseling Center, Welfare Organization, Ahvaz, Iran
  • Javad Mohammadi Asl Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  • Farideh Ghanbari Mardasi Mail department of midwifery, Shoushtar faculty of medical sciences, shoushtar, Iran
Con-rod dystrophy (CORD), Phosphodiesterase-6c (PDE6C) gene, Novel mutation, Next-generation sequencing, Non-stop mutation


Cone-rod dystrophy (CORD) is one of the most common genetic eye disorders. Recent genetic studies have demonstrated that it is a genetically heterogeneous disease among patients. Molecular genetic analysis of the 22 genes was performed in a family with Cone-rod dystrophy. Bioinformatics was applied for Next Generation Sequencing, and the variants were confirmed by Sanger sequencing. In this study, the nonstop mutation in the PDE6C gene (a normal stop codon is 859th codon of PDE6C located in exon 22 TAA (Stop) --> CAA (Gln) = Stop859Q) leads to a termination-site change and run-on into the 3' untranslated region (UTR) that predicts an extended protein which was found in the family. This mutation has not been described in patients with the CORD phenotype. Also, this is the first study indicating that a nonstop mutation in the homozygous state in PDE6C is responsible for the congenital recessive CORD phenotype.


1. Manitto MP, Roosing S, Boon CJ, Souied EH, Bandello F, Querques G. Clinical Utility Gene Card for: autosomal recessive cone-rod dystrophy. European Journal of Human Genetics 2015;23(12):1749.
2. Hamel CP. Cone rod dystrophies. Orphanet journal of rare diseases 2007;2(1):7.
3. Katagiri S, Hayashi T, Yoshitake K, Akahori M, Ikeo K, Gekka T, et al. Novel C8orf37 mutations in patients with early-onset retinal dystrophy, macular atrophy, cataracts, and high myopia. Ophthalmic genetics 2016;37(1):68-75.
4. Rahner N, Nuernberg G, Finis D, Nuernberg P, Royer-Pokora B. A novel C8orf37 splice mutation and genotype-phenotype correlation for cone-rod dystrophy. Ophthalmic genetics 2016;37(3):294-300.
5. Russell-Eggitt IM, Clayton PT, Coffey R, Kriss A, Taylor DS, Taylor JF. Alström syndrome: report of 22 cases and literature review. Ophthalmology 1998;105(7):1274-80.
6. Aleman TS, Cideciyan AV, Volpe NJ, Stevanin G, Brice A, Jacobson SG. Spinocerebellar ataxia type 7 (SCA7) shows a cone–rod dystrophy phenotype. Experimental eye research 2002;74(6):737-45.
7. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic acids research 1988;16(3):1215.
8. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nature methods 2010;7(4):248-9.
9. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nature protocols 2009;4(7):1073-81.
10. Grau T, Artemyev NO, Rosenberg T, Dollfus H, Haugen OH, Cumhur Sener E, et al. Decreased catalytic activity and altered activation properties of PDE6C mutants associated with autosomal recessive achromatopsia. Human molecular genetics 2010;20(4):719-30.
11. Hamby SE, Thomas NS, Cooper DN, Chuzhanova N. A meta-analysis of single base-pair substitutions in translational termination codons ('nonstop'mutations) that cause human inherited disease. Human genomics 2011;5(4):241.
12. Ameri A, Machiah DK, Tran TT, Channell C, Crenshaw V, Fernstrom K, et al. A nonstop mutation in the factor (F) X gene of a severely haemorrhagic patient with complete absence of coagulation FX. Thrombosis and haemostasis 2007;98(12):1165-9.
13. Pang S, Wang W, Rich B, David R, Chang YT, Carbunaru G, et al. A novel nonstop mutation in the stop codon and a novel missense mutation in the type II 3β-hydroxysteroid dehydrogenase (3β-HSD) gene causing, respectively, nonclassic and classic 3β-HSD deficiency congenital adrenal hyperplasia. The Journal of Clinical Endocrinology & Metabolism 2002;87(6):2556-63.
14. Burns ME, Baylor DA. Activation, deactivation, and adaptation in vertebrate photoreceptor cells. Annual review of neuroscience 2001;24(1):779-805.
How to Cite
Nasiri S, Talebi F, Mohammadi Asl J, Ghanbari Mardasi F. Identification of a Novel Non-Stop Mutation in PDE6C Gene in an Iranian Family With Con-Rod Dystrophy. Acta Med Iran. 58(6):297-300.
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