Pathogenic variant screening

So you have symptoms of retinitis pigmentosa (RP)? How could your DNA be sequenced to determine if there is a mutation in your RHO gene?

Which part of the genome should be sequenced?

RP is associated with the RHO gene, which is located on chromosome 3. Sequencing should be focused on this region of the genome, as this is where the gene of interest would be located.

Whole genome vs whole exome?

Whole genome sequencing investigates the entire genome. In contrast, whole exome sequencing focuses on the genetic sequence of the exons.

The majority of known pathogenic variants related to RP and dysfunction of the RHO gene are located within the exons of the gene. Therefore, it would be most effective to focus the sequencing on the exons of the gene, as this is where the pathogenic variant is most likely to be found if associated with RP-like symptoms.

Next generation sequencing (NGS) or Sanger sequencing?

NGS:

Can sequence the entire genome - Sanger focuses on smaller gene regions.
Is faster.
Cost effective.
Is more effective for the identification of DNA variants with a low frequency of occurrence.

While the RHO gene in particular is likely to be the focus of the sequencing investigation, NGS would be best, as it would also give the investigators the ability to investigate the rest of the genome for other potential pathogenic mutations.

You possess the pathogenic variant - what next?

The patient should first consult with a medical professional to discuss potential examination and treatment options or preventative measures. This could include checking the density of rod and cone photoreceptors in the retina through retinal imaging (reference 19). Patients could also consider genetic counselling to discuss the heritability of the condition.

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