Retinitis Pigmentosa (RP) is an inherited retinal dystrophy that is characterized by retinal degeneration and progressive vision loss in affected individuals. The disorder is caused by the gradual atrophy of the photoreceptor cells in the retina. Patients initially lose their rod photoreceptors, resulting in night vision loss (nyctalopia) and subsequently peripheral vision loss (tunnel vision). As the disease progresses, cone photoreceptors are affected, leading to problems with color vision, visual acuity and loss of the central visual field. Patients may also develop bone spicules in the fundus. Other symptoms of the disorder include the perception of blinking or shimmering lights (photopsia) and an aversion to bright light (photophobia). It is a heterogeneous disorder and as such, the age of onset can vary. Symptoms can present anytime from infancy to the third or fourth decade of life.
RP is found to affect about 1 in every 4000 individuals. Diagnosis of the disorder is based on ophthalmological examinations, electroretinogram studies to measure the electrical activity of the retinal photoreceptors, visual field tests to determine peripheral vision loss and genetic analysis to uncover mutations in known RP genes. Corrective visual aids, vitamin A supplementation and personalized vision therapy can help affected individuals cope with the disorder. It is also recommended that children diagnosed with RP undergo pre-symptomatic counselling to better prepare them for the physical ramifications of progressive vision loss.
While there are several forms of RP, the disorder RP12 follows an autosomal recessive pattern of inheritance. The disease is caused by mutations in the CRB1 gene. This gene encodes a protein that is believed to play a role in determining the structure and orientation of photoreceptors. Around 35 homozygous and compound heterozygous mutations in the CRB1 gene have been associated with retinitis pigmentosa. These are usually loss of function mutations that cause a shortage of normal CRB1 protein in the cells thus resulting in the progressive degeneration of photoreceptors.
Aldahmesh et al. (2009) attempted to identify the underlying genetic defects in 52 Retinitis Pigmentosa (RP) affected individuals from 17 Saudi families. The patients were diagnosed as having RP based on their gross retinal appearance and a detailed functional assessment. Family histories of all patients were obtained to classify them as sporadic or familial cases. Linkage analysis and homozygosity mapping studies resulted in the identification of CRB1 gene mutations in two families: a homozygous c. 3159T>G mutation resulting in a p.C1053W substitution affecting four members of a family and a homozygous c.80G>C mutation resulting in a p.C27F substitution affecting a single individual. Both missense mutations were found to affect highly conserved residues and neither of the mutations were found in 100 ethnically matched controls.
Monies et al. (2017) depicted the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, a 13-year-old female, suffered from microcephaly, fine/gross motor delay, speech delay, intellectual disability, learning disability, autistic features, ataxia, high blindness and retinitis pigmentosa. Whole exome sequencing helped identify a dual molecular diagnosis in this patient. A homozygous mutation (c.1898C>T, p.T633M) was found in exon 5 of the patient’s CRB1 gene, associated with retinitis pigmentosa 12, and a homozygous variant (c.346C>A, p.P116T) was uncovered in exon 4 of the ADIPOR1 gene, associated with intellectual disability (ID). Such dual molecular diagnoses were rare and only occurred in 1.5% of the cohort. Further, as the ADIPOR1 gene had previously been tentatively linked to ID, this report helped confirm its association with the disorder.
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