James Fasham

Some exciting openings in Exeter for clinical academics (professor and senior lecturer). Come and shape the future of translational genomic medical research in the South West! Lovely place to work, lovely people to work with, and freedom to pursue great science... www.linkedin.com/jobs/view/43...

We are looking to bring new talent and clinical academic leaders to Exeter and the South West. Freedom to explore your research ideas in a wonderful setting, do get in touch with @carolinefwright.bsky.social, @jamesfasham.bsky.social or I for an informal discussion.
@exeter.ac.uk

Job Advert - Clinical Academic Consultants in Genomic Medicine

Joint posts across the University of Exeter and Royal Devon, embedded in the NIHR Exeter BRC and a research-active, supportive Clinical Genetics Service.

📅 Apply by 22 March 2026
🔎 jobs.exeter.ac.uk → Genomic Medicine

Our new study defines a distinct #neurogenetic condition arising from recurrent structural variants at 16p13.3 palindrome.

Individuals show progressive ataxia, cognitive decline, and a characteristic MRI pattern with caudate & cerebellar atrophy.

#Genomics #RareDisease 🧵1/3

another great international collaboration with our friends in UK and Australia to which we could contribute, describing a very unique disease mechanism for a novel neurodegenerative disorder #genetics #raredisease @ajhgnews.bsky.social @jamesfasham.bsky.social @rdexeter.bsky.social

Palindrome-mediated 16p13.3 triplications cause a recognizable neurodegenerative disorder with ataxia - PubMed Complex neurodegenerative conditions have occasionally been associated with copy-number gains. Using microarray and genome sequencing on DNA samples from eleven individuals from nine unrelated families, we show that copy-number gains at 16p13.3 cause a severe, recognizable disorder characterized by …

Very grateful to colleagues including @rdexeter.bsky.social, @nihrexeterbrc.bsky.social, @stefanbarakat.bsky.social, the NHS Rare & Inherited Disease Genomic Network of Excellence, and to the patients and families who made this work possible. 🙏

Paper: pubmed.ncbi.nlm.nih.gov/41349538/

Long-read sequencing revealed inverted duplication–triplication structure not reliably detectable using standard clinical genomic assays 🔬

RNA-seq demonstrated significant ATP6VOC upregulation, implicating disrupted vacuolar H⁺-ATPase stoichiometry

Our new study defines a distinct #neurogenetic condition arising from recurrent structural variants at 16p13.3 palindrome.

Individuals show progressive ataxia, cognitive decline, and a characteristic MRI pattern with caudate & cerebellar atrophy.

#Genomics #RareDisease 🧵1/3

Amicia Phillips challenging traditional definitions of 'actionability' in the context of genomic #newbornscreening #ICoNS25

Follow up discussion:

A phenotypic spectrum / risk often exists below the level of a clinical "syndrome".

E. g. QT interval distribution

How does this affect our understanding of penetrance and expressivity?

Do parents understand this and how do we explain it if not?

Prof. Caroline Wright @UniofExeter explaining the challenges of quantifying penetrance of rare diseases in population cohorts at @ICoNSeqOrg #ICoNSs25

Beware ⚠️
- accidental inclusion of benign variants
- relying on limited phenotype data / codes which may be erroneous

Alistair Pagnamenta: rlReduced OI penetrance in @uk_biobank, implications for genomic newborn screening at #ICoNS25.

🦴 majority with P/LP variants have do not have multiple fractures

Impact on protein supported by proteomic data

👀 Preprint out today
www.medrxiv.org/content/10.1...

At #ICoNS25 meeting in London the last 2 days (sorry for absence of livetweets!)

Exploring the future of genomics as part of routine #NewbornScreening worldwide

ESHG suggestions from participants ESHG Feedback & suggestions Please add bullet points with suggestions for future ESHG conferences; think new/trending topics; speakers (amazing science and amazing presenters); formats; other options...

I loved it once again! Thanks for everyone making #eshg2025 happen!

#eshg2025 —> #eshg2026
Any suggestions for improvement ; ideas for topics and speakers?
Await the formal survey by @eshg.bsky.social but you can also let me know personally:

docs.google.com/document/d/1...

#MorbidGene (Test 2)

(Testing @diseasegenes.bsky.social)

#MorbidGene

(just testing the new 🤖 @diseasegenes.bsky.social bot)

#MorbidGene

(please see it's page, I will need to preauthorise all posters on BlueSky, API issues 🙄)

Also many thanks for the incredible - and ever growing - presence of colleagues, friends and collaborators from down under at #eshg2025 with many thanks to your SPC delegates — what a team 🇦🇺🇦🇺🇦🇺🇦🇺🇦🇺

Our amazing variant curator @njhenden.bsky.social presenting at #ESHG2025 - homozygous variant in SECISBP2 causing a severe perinatal cardiomyopathy - expanding the phenotype spectrum of selenoprotein deficiency disorders @nataliepstewart.bsky.social @amybakerlms.bsky.social

Look forward to seeing you in Exeter Lein ☺️

#eshg2025 it’s a wrap! We hope you enjoyed this year’s #eshg #hybridconference. Thank you for being part of it! We look forward to seeing you all at #eshg2026 in Gothenburg!

Congratulations Jingzhan ☺️

Mathilde DOYARD #ESHG2025

Starting with information that TBXAS1 disorders ⬆️ bone density

💊Could it be a target to treat bone fragility disorders such as OI?

thromboxane synthase (TXAS) inhibitors
in 🐭 studies
⬆️ bone formation
⬆️ biomechanical profiles

Patients next?

Edu Calpena #ESHG2025
@educalpena.bsky.social

Ectopic SIX3 expression underlies the craniofacial syndrome caused by deletions at the SIX2 locus

"Ectopic expression of SIX3 in the SIX2 territory"

2p21 deletions with TAD disruption shown below

Hristiana Lyubenova #ESHG2025

The absence of an enzyme-rescue metabolite as the cause of Catel-Manzke syndrome

A deep dive into uncovering the mechanism of this well-recognised condition

James Ware. The majority of cardiomyopathy cases do not have an identified monogenic cause.

#ESHG2025

If we ever needed a change we could do worse than EAHG : European Assembly of Human Geneticists?

James Ware introduced the term "recreational genomics" to refer to certain consumer genetic tests. And I love it.

#ESHG2025

The two sessions on penetrance and expressivity were among my top favourite seesions this year.

#ESHG2025

Current speaker Harry Wright in plenary session has been working in human genetics for 14 months. Another star in the making from the Exeter team #ESHG2025. Pointing out non coding aggregate signal in FGF18 for height, the gene has no coding signal (very constrained gene).