SNP Shot: Genomic Insights

Retinitis pigmentosa (RP) encompasses a group of inherited eye disorders that lead to progressive vision impairment. These conditions affect the retina, the light-sensitive layer at the back of the eye. In individuals with RP, the light-sensing cells of the retina gradually deteriorate, resulting in vision loss.

Typically, the initial symptom of RP is a decline in night vision, often noticeable during childhood. This difficulty seeing in low light conditions can make it challenging to navigate in the dark. As the disease progresses, blind spots develop in the peripheral (side) vision. These blind spots eventually merge, leading to tunnel vision. Over time, RP can affect central vision, which is crucial for tasks requiring detail, such as reading, driving, and facial recognition. Many adults with RP ultimately become legally blind.

The primary signs of RP are generally limited to vision loss. When RP occurs alone, it is classified as nonsyndromic. Researchers have identified several types of nonsyndromic RP, typically categorized by their inheritance pattern: autosomal dominant, autosomal recessive, or X-linked.

In less frequent cases, RP is part of a broader syndrome affecting other organs and tissues, known as syndromic RP. The most prevalent form of syndromic RP is Usher syndrome, characterized by the combination of vision and hearing loss that begins early in life. RP is also a feature of other genetic syndromes, including Bardet-Biedl syndrome, Refsum disease, and neuropathy, ataxia, and retinitis pigmentosa (NARP).

Inheritance:

RP frequently follows an autosomal dominant inheritance pattern. This means that a single copy of a mutated gene in each cell is enough to cause the disorder. In autosomal dominant RP, most affected individuals have a parent with the condition, and other family members are also affected.

RP can also be inherited in an autosomal recessive pattern. This requires both copies of a gene in each cell to carry mutations. The parents of someone with an autosomal recessive condition each carry one copy of the mutated gene, but they usually do not exhibit any signs or symptoms of the condition themselves.

Furthermore, RP can be inherited in an X-linked manner. The genes related to X-linked RP are located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), a single altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), mutations usually need to occur in both copies of the gene for the disorder to manifest. However, approximately 20% of females carrying only one mutated copy of the gene may still experience retinal degeneration and associated vision loss. Males typically experience more severe symptoms than females in X-linked inheritance. Fathers with X-linked traits cannot pass these traits on to their sons.

In 10 to 40 percent of RP cases, only one individual in a family is affected, classified as simplex. Determining the inheritance pattern in these cases can be challenging, as affected individuals may have no known affected relatives or may be unaware of other family members with the disease. Simplex cases can also arise from a new gene mutation not present in other family members.