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2024
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Retinitis pigmentosa
Disease Introduction
Retinitis Pigmentosa It is a chronic, progressive, hereditary and dystrophic retinal pigment disease, with a incidence rate of 1/3000. It is one of the main causes of blindness. The early symptoms of this disease are night blindness. As the disease progresses, central vision gradually decreases, mainly manifested as chronic progressive visual field loss, night blindness, pigmentary retinopathy, and abnormal electroretinogram, ultimately leading to complete blindness. Retinitis pigmentosa is mainly characterized by progressive degeneration of the retinal neuroepithelial layer, especially the rod cells responsible for low light vision, leading to night blindness, followed by gradual atrophy of various layers of tissues from the outside to the inside of the retina, accompanied by gliosis. The pigment epithelium also undergoes degeneration and hyperplasia, with visible loss or accumulation of pigment, and migrates towards the inner layer of the retina. The retinal vascular wall undergoes glassy degeneration and thickening, and even the lumen is completely occluded. Choroidal blood vessels may have varying degrees of sclerosis, with complete or partial disappearance of capillaries. The optic nerve can completely atrophy, and there is often gliosis on the optic rib, forming a membrane block that connects with the glial membrane in the retina. The wax yellow color of the optic disc seen under the ophthalmoscope is generally believed to be related to this.
Pathogenic genes and inheritance patterns
Retinitis pigmentosa has high genetic heterogeneity, including primary retinitis pigmentosa and retinitis pigmentosa syndrome. There are Usher syndrome and BBS syndrome associated with retinitis pigmentosa syndrome. There are over 80 known pathogenic genes, with common ones including CYP4V2, RHO, USH2A, RPGR, CRB1, and RP2. Retinitis pigmentosa can be inherited through autosomal dominant inheritance, autosomal recessive inheritance, X-linked inheritance, mitochondrial inheritance, and polygenic inheritance.
Treatment
There are no conventional effective drugs, but gene therapy drugs can be used for effective treatment. In 2017, the US FDA approved the gene therapy drug Luxturna for RPE65 gene mutations. It can not only treat Leber's congenital melanoma, but also treat other eye diseases such as retinitis pigmentosa caused by RPE65 gene mutations. The retinal pigment degeneration treatment drug developed by Zhongyin Technology has also entered the small sample clinical stage.
Case sharing
Clinical symptoms：The subject, male, 34 years old, was clinically diagnosed with crystalline retinitis pigmentosa.
Testing items：Genetic testing for ophthalmic genetic diseases (441 genes)
Test method ：Extract genomic DNA from the peripheral blood of the subject, construct a genomic library, capture relevant target gene exons and adjacent intron regions through probe hybridization, and enrich them. The enriched target gene fragments were sequenced using a high-throughput sequencing platform, and Sanger sequencing was used to validate the identified pathogenic variants.
Detection result ：Detect a pathogenic gene mutation that matches the clinical phenotype of the subject.
Note: According to the genetic variation classification criteria established by the American Society for Medical Genetics and Genomics (ACMG), mutations are divided into the following five types, with pathogenic mutations represented by pathogenic mutations; Likely pathogenic refers to a variant that may cause disease; Benign mutation; Like benign refers to a mutation that may be benign; Unknown significance refers to mutations with unclear meanings. AD stands for autosomal dominant inheritance; AR stands for autosomal recessive inheritance; X-linked represents X-linked inheritance.
Genetic analysis：(1) CYP4V2 gene mutations often cause crystalline retinitis pigmentosa, which is inherited in an autosomal recessive manner.
(2) The sample was tested and found to have a homozygous mutation in CYP4V2 c.802-8_810del17insGC. This mutation has been included in the HGMD database and has been reported as a pathogenic mutation in literature. The genetic diagnosis of the proband is consistent with the clinical phenotype.
Genetic counseling advice：(1) The subject carries a recessive homozygous mutation, originating from both the father and mother, who are carriers of the pathogenic mutation.
(2) The daughter of the test subject is a carrier of the disease causing gene, and in the future, her spouse will need to undergo genetic testing to determine if they are a carrier of the disease causing mutation. If the spouse is a carrier, their children have a 25% chance of getting sick; If the spouse does not carry the disease causing gene, their children will not get sick.
Reference：
1.Wada (2005) Am J Ophthalmol 139, 894
2.Gekka (2005) Ophthalmic Res 37: 262 [Additional case report]
3.Wang (2012) PLoS One 7: e33673 [Additional phenotype]
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CHIGENOVO Co., Ltd. is an ophthalmic gene therapy company, a national high-tech enterprise focusing on genetic diagnosis of genetic eye diseases and the development of gene therapy drugs. It is committed to providing "one-stop" services for patients with genetic eye diseases.
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