مقالات پذیرفته شده در هفتمین کنگره بین المللی زیست پزشکی
A Novel Homozygous Frameshift Insertion Mutation in The RPE65 Gene Causes Autosomal Recessive Retinitis Pigmentosa
A Novel Homozygous Frameshift Insertion Mutation in The RPE65 Gene Causes Autosomal Recessive Retinitis Pigmentosa
Nasrollah Saleh-Gohari,1Seyedeh Sepideh Aghamirli,2,*Marzieh Khalouei,3
1. Department of Medical Genetics, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran. 2. Department of Medical Genetics, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran. 3. Department of Medical Genetics, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Introduction: Retinitis pigmentosa (RP) is a group of hereditary deteriorations illustrated by progressive dysfunction of primarily rod photoreceptors followed by cone ones. RP without correlated systemic disease known as Typical RP has an estimated prevalence of 1:4000 globally. Patients developed typical RP manifest in the first or second decade of life with night blindness, progressive loss of the peripheral visual field followed by the loss of central vision, and final total blindness. Different inheritance patterns comprise autosomal dominant, autosomal recessive, and X-linked. Studies have reported at least 50 distinct genes to be related to RP. In this study, peripheral blood sample from patient with retinitis pigmentosa (RP), Whole-exome sequencing (WES) data, and Sanger sequencing data were integrated to assess the causing mutation of retinitis pigmentosa (RP) in an Iranian family.
Methods: Whole-exome sequencing (WES) performed on proband to screen pathogenic mutations and also Sanger sequencing performed on family members in order to confirm whether the detected mutation was related to the disease.
Results: This research demonstrated a significant frameshift insertion mutation that inherited from heterozygous unaffected carriers to affected individuals as a homozygous frameshift insertion mutation in the retinal pigment epithelium-specific 65 kDa protein (RPE65) gene (NM_000329: exon9: c.886dupA: p.R296fs). Therefore, this mutation has been identified as the cause of autosomal recessive retinitis pigmentosa (ARRP).
Conclusion: In conclusion, homozygous frameshift insertion mutation (NM_000329: c.886dupA: p.R296fs) in exon9 of RPE65 also known as retinoid isomerohydrolase is reported as the genetic cause of retinitis pigmentosa for the first time.