ARVO 2024 Highlight: New Gene Linked to RP in People with African Ancestry

A team of genetic researchers from the UK, US, and Switzerland has identified a mutation in the gene TMEM216 as a common cause of retinitis pigmentosa (RP) in people with African ancestry. The team estimates that approximately 20-30 percent of all RP patients with African descent are homozygous for this mutation — that is, both copies of their TMEM216 gene have the mutation, leading to RP. People have about 23,000 pairs of genes in most every cell in their bodies and both gene copies in a pair must be mutated for recessive disease to occur.

The genetic breakthrough was reported during a poster session at the 2024 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) held May 5-9 in Seattle.

The team was led by Andrew Webster, MBBS, professor of molecular ophthalmology at University College London, and Radha Ayyagari, PhD, chief of Ophthalmic Molecular Genetics at Shiley Eye Institute, University of California, San Diego.

The breakthrough was funded through the Foundation’s $2.5 million Elusive Genes research project, which includes Dr. Ayyagari; Eric Pierce, MD, PhD, and Kinga Bujakowska, PhD, at Mass Eye and Ear; and Stephen Daiger, PhD, and Lori Sullivan at University of Texas Health in Houston.

The researchers used whole genome sequencing to evaluate all the genetic information of 2,316 inherited retinal disease (IRD) patients from the 100K UK Genomes Project (100KGP) and 672 IRD patients from the NIHR Bioresource for Rare Disease in the UK (NIHRRD). In the 100KGP group, the investigators found 18 genetically unsolved RP patients with African ancestry who had two copies of the c.-69G>T mutation in TMEM216. In the NIHRRD group, they identified six genetically unsolved RP patients with African descent who had two copies of that same mutation.

In addition, 10 genetically unsolved African American patients with RP evaluated by Dr. Pierce had two copies of the same TMEM216 mutation. 

“Our discovery is important because the retinal disease research community lacks clinical and genetic information for many people with retinal conditions who have non-European descent. Because these patients and families are under-represented, we have a more difficult time diagnosing their retinal conditions,” says Dr. Ayyagari. “As a relatively common cause of RP in Africans, the TMEM216 mutation was hiding in plain sight. Most important, the discovery will help us genetically diagnose many more RP patients with African ancestry.”

Dr. Ayyagari also said that 29 individuals from nine families with Pakistani ancestry were found to have the TMEM216 mutation c.-69G>A, which is at the same location as the prevalent African mutation but is a different change in nucleotides.

Dr. Ayyagari’s team is conducting additional lab studies to confirm that the TMEM216 mutations are causing retinal degeneration.