New genetic findings can shape future treatments and improve outcomes for African
and Pakistani retinitis pigmentosa patients

Researcher Radha Ayyagari, PhD at the UC San Diego Health, Shiley Eye Institute and the
Viterbi Family Department of Ophthalmology, and international collaborators conducted a
global study that suggests a genetic link between African and Pakistani populations and
Retinitis Pigmentosa (RP .)

Retinitis Pigmentosa, a genetic condition, is a disease that changes how the retina
responds to light and makes it hard to see. RP symptoms include night blindness, tunnel
vision, loss of central vision and problems with color vision which can eventually lead to
legal blindness. According to the study, it is estimated that RP affects approximately 1 in
2,500 to 4,000 individuals worldwide.

This study published on August 26, 2024 online in The American Journal of Human
Genetics (AJHG), is the first to identify a genetic link between African and Pakistani descent
populations and RP.

“Our study specifically describes the major causative mutations in two historically
understudied populations- African and Pakistani. Our study is also estimated to explain the
cause of RP in about 20% or more cases of RP in patients of African ancestry,” said
Ayyagari.

Researchers analyzed the expression of disease gene TMEM216 in the blood samples of
participants with RP . Specifically in individuals of African ancestry, reduced TMEM216
expression was identified as potentially leading to photoreceptor degeneration, which is a
symptom of retinitis pigmentosa.

Through genome analysis of individuals with RP, two rare nucleotide substitutions at the
same DNA genomic location were identified in individuals of African and South Asian
ancestry. This pinpoints unique RP gene mutations only found in these populations.
This studies participant data came from the whole genome sequence (WGS) of individuals
from UK cohort Genomics England 100,000 Genomes Project (UK100k). The main cohort
consisted of 2,316 participants (from 2038 families) with inherited retinal degeneration
(IRD). In addition to data the UK100k cohort two families of Pakistani origin were also
included. All available participants also underwent an ophthalmic examination, and
detailed clinical and familial history was collected.

“The findings from this study represent a breakthrough in our understanding of the genetic
link between RP and patients with African and Pakistani ancestry,” said Ayyagari. “We can
now work to better transform our treatment and care for RP patients with African and
Pakistani ancestry around the world.”

Co-authors of this study include: Samantha Malka Moorfields, Eye Hospital NHS Trust, and
University College London; Pooja Biswas and Anne-Marie Berry, UC San Diego; Riccardo
Sangermano, Harvard Medical School; Mukhtar Ullah, Institute of Molecular and Clinical
Ophthalmology Basel (IOB) and University of Basel; Siying Lin, Moorfields Eye Hospital
NHS Trust and University College London; Matteo D’Antonio, UC San Diego; Aleksandr
Jestin, University College London; Xiaodong Jiao, National Institutes of Health; Mathieu
Quinodoz, Institute of Molecular and Clinical Ophthalmology Basel (IOB), University of
Basel, and University of Leicester; Lori Sullivan, University of Texas Health Science
Center; Jessica Gardner, University College London, Emily Place, Harvard Medical School;
Michel Michaelides, Moorfields Eye Hospital NHS Trust and University College London;
Karolina Kaminska, Institute of Molecular and Clinical Ophthalmology Basel (IOB) and
University of Basel; Omar A. Mahroo, Moorfields Eye Hospital NHS Trust, University College
London, St Thomas’ Hospital and King’s College London; Elena Schiff and Genevieve
Wright, Moorfields Eye Hospital NHS Trust and University College London; Francesca
Cancellieri, Institute of Molecular and Clinical Ophthalmology Basel (IOB) and University of
Basel; Veronika Vaclavik, Hôpital Ophtalmique Jules-Gonin; Cristina Santos, Instituto de
Oftalmologia Dr. Gama Pinto (IOGP) and Universidade NOVA de Lisboa; Atta Ur Rehman,
Hazara University; Sudeep Mehrotra and Hafiz Muhammad Azhar Baig, Harvard Medical
School; Muhammad Iqbal, The Islamia University of Bahawalpur; Muhammad Ansar,
Muhammad Ansar; Luisa Coutinho Santos, Instituto de Oftalmologia Dr. Gama Pinto
(IOGP); Ana Berta Sousa, Centro Hospitalar e Universitário de Lisboa Norte (CHULN) and
Hospital de Santa Maria; Viet H Tran Hôpital Ophtalmique Jules-Gonin; Hiroko Matusi and
Anjana Bhatia, Harvard Medical School; Muhammad Asif Naeem, University of the Punjab;
Shehla J. Akram, Akram Medical Complex; Javed Akram, Allama Iqbal Medical Research
Center and Jinnah Hospital; Sheikh Riazuddin, Jinnah Burn and Reconstructive Surgery
Center, University of Health Sciences; Carmen Ayuso, Universidad Autónoma de Madrid
(IIS-FJD, UAM); Eric Pierce, Harvard Medical School; Alison Hardcastle, University College
London; S. Amer Riazuddin, Johns Hopkins University School of Medicine; Kelly A. Frazer,
UC San Diego; J. Fielding Hejtmancik, National Institutes of Health; Carlo Rivolta, Institute
of Molecular and Clinical Ophthalmology Basel (IOB), University of Basel and University of
Basel; Kinga Bujakowska, Harvard Medical School; Gavin Arno, Moorfields Eye Hospital
NHS Trust, University College London and UC San Diego; Andrew R Webster, Moorfields
Eye Hospital NHS Trust and University College London; and Radha Ayyagari, UC San Diego