Finnish founder variant
XXYLT1 retinal dystrophy, and the change about one Finn in eighty carries
In 2026 researchers in Oulu, working with FinnGen and the UK’s 100,000 Genomes Project, tied the gene XXYLT1 to an inherited retinal dystrophy. The change behind it in Finland, NM_152531.5:c.505-1G>C (rs201922399), is common for a disease-causing change: roughly 1 in 80 people in Finland carry this change (gnomAD v4.1); in other Europeans it is about 190 times rarer. Two copies were found in people with a cone-rod or macular dystrophy that usually began in adulthood; one copy is carrier status. A whole-genome file can show whether you carry it. A consumer chip export cannot.
What the 2026 study found
The team compared 540 people in FinnGen with an inherited retinal disease on record against 473,945 without, and looked specifically for changes that matter only when a person carries two copies. Thirteen places in the genome passed the usual significance bar. Four were new, and the strongest new one, at p = 9.7 × 10−20, was a single change in XXYLT1.
They then tested 49 patients at Oulu University Hospital whose retinal disease had no genetic explanation, and found five more people with two copies, from four families. RNA from patients showed what the change does: it sits on the last letter before the gene’s second exon, cells skip that exon when they read the gene, and the gene stops working. In the UK two further patients carried two copies of a different XXYLT1 change, which points at the gene itself rather than at something near it.
Before this, XXYLT1 was not known to cause any human disease. The authors conclude that it belongs on clinical gene panels for inherited retinal disease.
Who carries it
This is a founder change: it traces back to one ancestor and spread as Finland’s population grew from a small base, the same history that gave Finland its Finnish Disease Heritage. In gnomAD v4.1 the change sits on 0.63 percent of Finnish chromosomes and is 191 times rarer in other Europeans. In FinnGen 5,069 of 520,210 participants carried one copy and 19 carried two. The authors estimate that around 218 people in Finland carry two copies.
Some people with two copies in FinnGen had no retinal diagnosis on record. That can mean the disease had not started yet, since it often begins in middle age, or that not everyone with two copies develops it. The study cannot yet say which.
One copy, two copies
One copy
This is carrier status. The condition is recessive, so one working copy of XXYLT1 is enough, and carrying one changed copy is not known to affect your own eyesight. It matters for children: if your reproductive partner also carries it, each child has a 1-in-4 chance of inheriting two copies. With one Finn in eighty to one hundred carrying it, two carriers meeting is not rare. Testing the partner for this one change is the direct way to find out.
Two copies
For this change, two copies have been linked to a cone-rod or macular dystrophy: a slow loss of central and colour vision, sometimes with fluid or splitting in the layers of the macula. It usually shows in adulthood. In the study the median age at diagnosis was 38, ranging from 13 to 76. The same study found people with two copies who had no retinal diagnosis on record, so two copies do not make the condition certain or fix when it would begin. An ophthalmologist's examination, with retinal imaging, is what shows whether the retina is affected, and a genetics service can confirm the finding with a targeted test.
None of this is a diagnosis. A result in your file is a match against a published study, and a validated, gene-targeted test is what confirms it.
Which files can show it
| Your file | Can it show this change? |
|---|---|
| A whole-genome gVCF | Yes, and it also records that the gene was covered, so a clear result means the sequencing looked there |
| A whole-genome plain VCF | Yes if you carry it. If you don’t, the file is silent either way |
| A chip export23andMe, AncestryDNA, MyHeritage, FamilyTreeDNA, Living DNA | No. The arrays don’t include this position |
| A low-pass genome1x to 2x, such as recent MyHeritage kits | No. It is read like a chip, without the carrier panel |
We checked 14 real chip exports, 23andMe versions 3 to 5 among them, and none carries the position at 3:195,226,857 (GRCh38). Not sure what you have? The free file check tells you in your browser, and supported files explains each type.
How the report shows it
The carrier section of a whole-genome report normally lists only changes that ClinVar, the public archive of laboratory classifications, records as pathogenic with at least one review star. This change is too new for that: ClinVar had no record of it when we last checked on 2026-09-28. So it sits on a short list we keep for founder changes a peer-reviewed study has shown to cause disease, each checked against four conditions: the study was published, it showed the change switches the gene off, it found patients with two copies beyond the original analysis, and ClinVar has not classified it yet.
On your report it appears under its own heading, “Published research, not yet in ClinVar”, with the study named on the result. We match it only at its exact position and letter, never anywhere else in the gene, and we rank it below the ClinVar-classified findings. When ClinVar classifies it, the ClinVar record takes over.
Common questions
What is XXYLT1 retinal dystrophy?
An inherited disease of the retina linked in 2026 to the gene XXYLT1. People with two copies of the Finnish founder change NM_152531.5:c.505-1G>C developed a cone-rod or macular dystrophy: a gradual loss of central and colour vision, sometimes with fluid or splitting in the layers of the macula. It usually appeared in adulthood, at a median age of 38 when diagnosed. Before this study XXYLT1 had not been tied to any human disease.
How common is the XXYLT1 founder variant in Finland?
Between about 1 in 80 and 1 in 100 people in Finland carry one copy, depending on the dataset: gnomAD v4.1 puts its frequency in Finns at 0.63 percent of chromosomes, 191 times its frequency in other Europeans. The study's authors estimated that around 218 people in Finland carry two copies.
Can 23andMe or AncestryDNA raw data show XXYLT1 c.505-1G>C?
No. The change is not on the consumer genotyping arrays: none of the 14 real chip exports we checked, from 23andMe, AncestryDNA, MyHeritage, FamilyTreeDNA and Living DNA, carries the position. A whole-genome file does, which is why the finding is part of the whole-genome report only.
I carry one copy. Will it affect my eyesight?
Carrying one copy is not known to affect the carrier's own eyes. The condition is recessive, so it arises only when both copies of the gene carry a disease-causing change. One copy matters for family planning: if a partner also carries it, each child has a 1-in-4 chance of inheriting two copies.
Why is it reported when ClinVar has not classified it?
ClinVar is where laboratories record their classifications, and for a change found in 2026 no laboratory has done so yet. We normally report only what ClinVar classifies as pathogenic. This change is one of a short list reported from its published study instead, because the study showed that it switches the gene off and found it in two copies in patients from several families. The report says so on the result, names the study, and treats it as lower confidence than a ClinVar classification.
XXYLT1 is one of the carrier conditions in the whole-genome report, €39.
Sources
- Kraatari-Tiri M, Ishtiaq H, et al. XXYLT1 and Mendelian Retinal Dystrophy. JAMA Ophthalmology. 2026;144(9):827–836. Open access under CC BY 4.0; the figures on this page are quoted from it.
- We want to acknowledge the participants and investigators of the FinnGen study. Kurki MI et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;613:508–518.
- gnomAD v4.1: 3-195226857-C-G
- MedlinePlus Genetics: cone-rod dystrophy