Genetic counseling for pre-implantation genetic testing of monogenic disorders (PGT-M)

Rare Genetic Eye Conditions Not So Rare After All: SNEC Study

SINGAPORE – Inherited retinal diseases (IRD) are not as rare here as previously thought, a research programme at the Singapore National Eye Centre (SNEC) has found.

IRDs are a group of genetic eye conditions which cause gradual and sometimes complete vision loss. The vast majority of such diseases have no cure.

"When you read about these conditions, you will hear that these are extremely rare. But when we started being a bit more systematic in identifying these patients, we found that actually it's far more common than we would have thought, and often under-diagnosed," said Dr Beau Fenner, one of the programme's researchers.

"To be honest, no one really knows how many individuals in Singapore have inherited retinal disease," he added. But he put the number at between 3,000 and 5,000 people.

IRDs are quickly becoming an important group of eye diseases tackled in Singapore, and efforts to unpack these often poorly understood conditions are growing.

With genetic eye conditions now the primary cause of blindness among working-age adults in developed nations, SNEC in October also established its Ocular Genetics Service (OGS) to offer specialised care for this group of patients.

Complementing each other, the OGS runs concurrently with the research programme by SNEC's research arm, the Singapore Eye Research Institute. Ongoing since March 2021, the institute's programme has more than 1,200 participating patients.

"Our clinical research programme is probably the largest of its kind in the region," Dr Fenner said, adding that around 90 per cent to 95 per cent of SNEC's IRD patients have been registered in the programme.

Participants include SNEC's new and existing IRD patients, as well as their relatives when relevant. The programme collects information such as participants' clinical records which are relevant to their condition.

Beyond guiding research for potential treatments, the programme's collection of patient records helps doctors reach out to individuals with IRD as new treatments emerge, Dr Fenner said.

This is especially helpful, as some patients may have chosen not to return for follow-ups at SNEC, given that there is no cure for their condition.

A key goal of the research programme is to identify the most common inherited retinal conditions here.

"If we're going to spend a lot of time and money developing therapies for inherited retinal conditions, we should be looking at those which matter to Singapore," said Dr Fenner.

He estimates that SNEC, which sees roughly 50 per cent of Singapore's subsidised patient volume, sees only about 20 per cent to 30 per cent of all people with retinal dystrophy here.

The study has since identified retinitis pigmentosa as the most significant condition, accounting for about 50 per cent of all inherited retinal diseases in Singapore.

While there are many gene mutations that could cause the disease, Dr Fenner said a mutation in the EYS gene is the most common cause for the condition in Singapore and particularly prevalent in individuals of southern Chinese descent.

One hope researchers have for the programme is to better equip clinicians to recognise these conditions and decode their inheritance patterns, which enables them to provide more holistic advice to affected patients.

Dr Fenner said: "When we first started this work, a lot of clinicians thought we didn't have all these different interesting inherited retinal conditions in Singapore – but that's turned out not to be the case.

"These conditions are all here. It's just whether there are people able to diagnose them. Some of these conditions are quite challenging to diagnose."

In contrast to the United States or Europe, where similar research efforts have been going on for decades, Dr Fenner said there is still not much known about genetic eye diseases in this part of the world.

"It's relatively recent here in South-east Asia, and so we're still in the beginnings of our research journey to understand what matters for Singaporeans," he said.

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Unlocking The Genetics Of Blindness: New Hope For Sufferers Of Inherited Retinal Diseases

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69 New Genetic Causes Of Rare Diseases Identified

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A landmark study has found 69 previously unidentified genetic determinants of rare disease, including uncommon forms of kidney disease and diabetes. 

The breakthrough research, involving the University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, uses a new analytical approach for identifying the genetic basis of rare diseases, which could diagnose more cases and help develop new treatments for patients.

Rare diseases collectively affect between four and six per cent of people worldwide. Despite advances in genetic testing, most genetic variants that lead to disease remain unknown resulting in around 80 per cent of people with a rare disease being undiagnosed even after genomic sequencing. 

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To address this issue, an international team of researchers developed an analytical framework for identifying genetic causes of Mendelian diseases (mutations in one gene), known as variant gene burden analysis.

The team then applied this framework to the genetic records of 34,851 people and their family members (72,690 genomes in total) from Genomics England's 100,000 Genomes Project. 

The study, published in Nature, identified genetic variants in 69 genes not previously known to be associated with any disease. In 30 of these cases, the new genetic findings were supported by existing experimental evidence, thereby confirming the accuracy of the novel approach.

Importantly, the strongest overall genetic and experimental evidence supported newly discovered genetic variants for rare forms of kidney disease, diabetes, schizophrenia, epilepsy, Charcot-Marie-Tooth (CMT) disease, and anterior segment ocular abnormalities (developmental defects or structural issues within the front part of the eye).

Professor Albert Ong, Professor of Renal Medicine at the University of Sheffield and Consultant Nephrologist and Clinical Lead for Kidney Genetics at Sheffield Teaching Hospitals NHS Foundation Trust, said: "Sheffield has a long and proud history of kidney disease research. This paper highlights the power of unlocking genetics through the 100,000 Genomes Project to provide hope to millions of people suffering with undiagnosed rare diseases by discovering many new genes for diseases ranging from epilepsy, diabetes, brain disorders to cystic kidney disease."

Professor Ong, who gave his expert opinion on the 22 genes linked to rare kidney diseases found in the study, added: "Gene discovery is the first step towards diagnosis, a clearer understanding and the eventual development of new treatments to cure or slow disease. This is great news for patients and their families as it will provide them with an opportunity to be given a clear diagnosis. I am also proud that many patients from Sheffield contributed to this important UK project." 

Reference: Cipriani V, Vestito L, Magavern EF, et al. Rare disease gene association discovery in the 100,000 Genomes Project. Nature. 2025. Doi: 10.1038/s41586-025-08623-w

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