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A gene is linked to retinitis pigmentosa. An international team coordinated by three Italian researchers—Viviana Cordeddu of the Istituto Superiore di Sanità, Marco Tartaglia of the Bambino Gesù Children's Hospital in Rome, and Lucia Ziccardi of the Bietti IRCCS Foundation in Rome—with the involvement of numerous European and US centers, has identified the Prkcz gene as a new genetic cause of retinitis pigmentosa (RP), one of the most common hereditary retinal diseases and a leading cause of severe genetic vision loss.
The study, published in 'Jama Ophthalmology', expands knowledge of the genetic and molecular basis of the disease, opening new perspectives for diagnosis and treatment.
Retinitis pigmentosa, the ISS explains on its website, comprises an extremely heterogeneous group of inherited retinal diseases, with onset in both childhood and adulthood. The first signs may manifest as marked difficulty seeing in low light, known as night blindness, and a progressive reduction in peripheral vision.
As the disease progresses, the visual field may narrow, resulting in a characteristic tubular vision, with the patient retaining predominantly central vision. Increased sensitivity to light and glare, a reduction in the ability to perceive contrast, and, in more advanced forms and depending on the involvement of the central retina, a progressive reduction in visual acuity may also occur.
The clinical evolution is, however, variable and depends on the specific genetic form and the individual characteristics of the patient.
By sequencing the genomes of patients from several countries, scientists identified pathogenic variants in the Prkcz gene in 10 families, demonstrating that alterations in this gene can cause a novel recessive form of retinitis pigmentosa. Most of the patients studied had an apparently isolated form of the disease, with onset in adulthood. This finding is considered particularly significant because some forms of retinitis pigmentosa can manifest many years after birth and, in the absence of a clear family history, make identifying the genetic cause more difficult.
Functional studies conducted by the research group have also shown that the identified variants compromise the normal function of the Pkcζ protein, involved in important cellular processes. Alterations in this protein can interfere with the mechanisms necessary for the maintenance and survival of photoreceptors, the retinal cells responsible for transforming light into visual signals. "The identification of new genes associated with the disease," the authors propose, "may help improve the diagnostic process, allowing in some cases to link the patient's clinical picture to a specific genetic cause. It may also provide families with more precise information on the origin of the disease, possible transmission mechanisms, and the possible presence of other affected family members." The new discovery also represents "a starting point for further studies on the cellular mechanisms involved in photoreceptor degeneration. Understanding these mechanisms may contribute, in the long term, to the search for targeted therapeutic strategies, in a context in which gene therapy is emerging as a potential approach for several ocular diseases."
"Despite the extraordinary advances in genetics in recent years," says Cordeddu, ISS researcher and first author of the study, "a significant proportion of patients with retinitis pigmentosa still remain without a molecular diagnosis. The identification of Prkcz allows us to provide answers to new families and contributes to a better understanding of the biological mechanisms underlying retinal degeneration." For Tartaglia, head of the Molecular Genetics and Functional Genomics Research Unit at the Bambino Gesù Children's Hospital and coordinator of the study, "the identification of new genes associated with retinitis pigmentosa represents an important step forward in understanding the genetic basis and biological mechanisms underlying the disease. The discovery also opens new perspectives for the development of more accurate diagnostic tools and increasingly targeted therapies in the future." Monica Varano, scientific director of the Bietti IRCCS Foundation, notes that "our institute has been recognized as a reference center for rare ocular diseases, and our collaboration with the ISS and the Bambino Gesù Children's Hospital on these issues is long-standing."
"It is important to emphasize," the ISS news release states, "that the identification of Prkcz as the genetic cause of the disease does not currently correspond to the availability of a specific therapy for this form of retinitis pigmentosa. This finding represents, first and foremost, an advance in the diagnosis and biological understanding of the disease, laying the foundation for future research."
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