Two novel PDE6C gene mutations in Chinese family with achromatopsia

ABSTRACT

Background: Achromatopsia (ACHM) is an inherited retinal disease affecting the cone cell function. To date, six pathogenic genes of ACHM have been identified. However, the diagnostic and therapeutic methods of this disorder remain limited. Herein, to characterize the clinical features and genetic causes of three affected siblings in a Chinese family with ACHM, we used target next-generation sequencing (NGS) and found new pathogenic factors associated with ACHM in this family.

Materials and methods: Three patients with ACHM and three healthy family members were included in this study. All participants received comprehensive ophthalmic tests. NGS approach was performed on the patients to determine the causative mutation for this family. The silico analysis was also applied to predict the pathogenesis of identified mutations.

Results: Genetic assessments revealed compound heterozygous mutations of the PDE6C gene (c.1413 + 1 G > C, c.305 G > A), carried by all three patients. Both mutations were novel and predicted to be deleterious by six types of online predictive software. The heterozygous PDE6C missense mutation (c.305 G > A) was found from the mother and the heterozygous PDE6C splice site mutation (c.1413 + 1 G > C) was found in the father and all the children. All patients in the family showed typical signs and symptoms of ACHM.

Conclusions: We report novel compound heterozygous PDE6C mutations in causing ACHM and further confirm the clinical diagnosis. Our study extends the genotypic spectrums for PDE6C-ACHM and better illustrates its genotype–phenotype correlations, which would help the ACHM patients with better genetic diagnosis, prognosis, and gene treatment.

KEYWORDS:

• PDE6C
• compound heterozygous mutations
• achromatopsia

Acknowledgments

The authors thank all patients and their family members for their participation.

Declaration of interest statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Supplementary material

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Additional information

Funding

This work was supported by the National Natural Science Foundation of China under grant number 81760180; and the Key R & D Plan Project of Ningxia Hui Autonomous Region under grant number 2017BY086.