Astrid Foundation

Xq25 · STAG2 · cohesinopathies

Some genes cause harm
not when they break —
but when there is
too much of them.

Astrid supports laboratory research into STAG2 duplication syndrome: a rare condition in which an extra copy of a single gene disrupts how neurons switch other genes on and off during brain development.

The research programme Learning centre
Fig. 1 Cohesin reels DNA into loops, deciding which regulatory switches reach which genes. STAG2 is one of its interchangeable parts.

Both directions cause harm

For most genes an extra copy is absorbed without consequence. A few are dosage-sensitive: the amount of protein must stay inside a narrow window. Too little causes one disorder. Too much causes another.

STAG2 sits at the centre of this problem. It forms part of cohesin, the ring-shaped complex that folds the genome into loops — and it is also a tumour suppressor. So the goal of treatment is not to switch it off, but to nudge it partway back toward normal, and no further.

That constraint — precision rather than force — shapes every decision in the field.

too little too much healthy window amount of protein → severity
Fig. 2 The dosage window.

The gap

Rare, collectively, is not rare at all

Rare diseases are individually uncommon and collectively ordinary. Most are genetic, most begin in childhood, and almost none have a treatment — because no commercial market exists to fund one.

10,000+
rare diseases affecting people in the United States NIH GARD
<5%
have an approved treatment NIH GARD
72%
are genetic in origin EURORDIS
70%
begin in childhood EURORDIS

For STAG2 duplication syndrome specifically

28
affected males in the largest published series Kumar 2015
0
interventional clinical trials ClinicalTrials.gov
0
therapies approved for this condition ClinicalTrials.gov

A condition this rare will never attract conventional drug development. That is not a scientific problem — the biology is tractable and the tools exist. It is a funding and coordination problem, and it is the reason work like this depends on families and research hospitals rather than industry.

Sources. Cohort figure: Kumar et al., Human Molecular Genetics 2015;24(25):7171–81 — PMID 26443594 (“15 affected individuals from 6 different families and 13 singleton cases, 28 affected males in total”). Trial counts: ClinicalTrials.gov API, interventional studies for STAG2, Xq25 duplication and cohesinopathy — all returned zero, queried 28 July 2026. Rare-disease figures: NIH GARD and EURORDIS. Figures are quoted as published; counts are point-in-time and may change.

Research partner

The programme

The laboratory work is led by Dr. Zhenya Ivakine in Genetics & Genome Biology at The Hospital for Sick Children in Toronto — a centre built around precisely this problem: definitive answers and tailored treatment for children whose conditions are too rare for conventional drug development to reach.

  1. 01

    Understanding the problem

    Studying how excess STAG2 affects brain cells — identifying which genes are disrupted, and how that translates into effects on cognition, movement and speech.

  2. 02

    Finding solutions

    Testing medications already approved for other conditions, whose safety in humans is established, for any that restore balance in affected cells — alongside genetic approaches to lower STAG2 or bypass its effects.

  3. 03

    Modelling and validation

    Building laboratory models that reproduce the condition, used to validate promising candidates and establish whether they are worth carrying toward clinical trials.

Astrid Foundation supports this research. It is not a registered charity and does not solicit donations.

Open resource

A guide to the science, from first principles

We could not find a public educational resource on STAG2 duplication syndrome anywhere, so we wrote one. Eight parts, thirty-three modules — from what a gene is, through cohesin and gene dosage, to how laboratory models and drug screens actually work.

No biology background needed. Every technical term is explained where it first appears, and there is a full glossary.

Written for families facing a new diagnosis, clinicians meeting their first case, and researchers considering the field.

Open the learning centre
  1. 01 Foundations — DNA, inheritance, and gene dosage
  2. 02 The condition — cohesin, loop extrusion, the evidence
  3. 03 Reading the evidence — papers, databases, precedent
  4. 04 The laboratory — cell models, controls, readouts
  5. 05 Therapeutics — the modality options and their trade-offs
  6. 06 From lab to child — regulation and outcome measures
  7. 07 For families — running a research programme
  8. 08 Reference — glossary and reading list

Collaborators

The research workspace holds the literature library, active hypotheses, experimental records and the learning centre. Access is limited to named collaborators.

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Researchers working on STAG2 dosage biology or cohesinopathy models are welcome to get in touch.