James Fasham
@jamesfasham.bsky.social
🧬👨⚕️Academic Consultant in Clinical Genetics 💬 ESHG Social media chair. 🤖 @DiseaseGenes bot creator #Genetics #Genomics #RareDisease
Amicia Phillips challenging traditional definitions of 'actionability' in the context of genomic #newbornscreening #ICoNS25
October 24, 2025 at 1:30 PM
Amicia Phillips challenging traditional definitions of 'actionability' in the context of genomic #newbornscreening #ICoNS25
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
Beware ⚠️
- accidental inclusion of benign variants
- relying on limited phenotype data / codes which may be erroneous
October 24, 2025 at 11:03 AM
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
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...
🦴 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...
October 24, 2025 at 10:46 AM
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...
🦴 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
Exploring the future of genomics as part of routine #NewbornScreening worldwide
October 24, 2025 at 10:34 AM
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
Exploring the future of genomics as part of routine #NewbornScreening worldwide
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?
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?
May 27, 2025 at 10:27 AM
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?
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
@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
May 27, 2025 at 10:10 AM
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
@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
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
May 27, 2025 at 9:48 AM
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
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
Eike Bolmer #ESHG2025
🩻 Bone2Gene-Screen: AI-Augmented Early Detection of Rare Bone Diseases
✋Using hand x-ray
🔴 Occlusion testing allows important region within the image to be defined (see below)
🩻 Bone2Gene-Screen: AI-Augmented Early Detection of Rare Bone Diseases
✋Using hand x-ray
🔴 Occlusion testing allows important region within the image to be defined (see below)
May 27, 2025 at 9:33 AM
Eike Bolmer #ESHG2025
🩻 Bone2Gene-Screen: AI-Augmented Early Detection of Rare Bone Diseases
✋Using hand x-ray
🔴 Occlusion testing allows important region within the image to be defined (see below)
🩻 Bone2Gene-Screen: AI-Augmented Early Detection of Rare Bone Diseases
✋Using hand x-ray
🔴 Occlusion testing allows important region within the image to be defined (see below)
Vicente Yepez #ESHG2025
Rare Disease multi-OMICs Solvathons - a disease solving hackathon
- make sure you have consent to share
Integrated multi-omics in parallel is best
DNA-RNA & DNA-proteomic parallel approaches both ⬆️ diagnoses 10-15% (many refs)
Rare Disease multi-OMICs Solvathons - a disease solving hackathon
- make sure you have consent to share
Integrated multi-omics in parallel is best
DNA-RNA & DNA-proteomic parallel approaches both ⬆️ diagnoses 10-15% (many refs)
May 27, 2025 at 8:05 AM
Vicente Yepez #ESHG2025
Rare Disease multi-OMICs Solvathons - a disease solving hackathon
- make sure you have consent to share
Integrated multi-omics in parallel is best
DNA-RNA & DNA-proteomic parallel approaches both ⬆️ diagnoses 10-15% (many refs)
Rare Disease multi-OMICs Solvathons - a disease solving hackathon
- make sure you have consent to share
Integrated multi-omics in parallel is best
DNA-RNA & DNA-proteomic parallel approaches both ⬆️ diagnoses 10-15% (many refs)
Kym Boycott #ESHG2025
Disease-Gene discoveries are falling 😲
Don't tell @DiseaseGenes bot! 🤖
#MorbidGene
In all seriousness, I suspect that conditions associated with each gene are growing - we are in a phase of understanding of gene pleiotropy
Disease-Gene discoveries are falling 😲
Don't tell @DiseaseGenes bot! 🤖
#MorbidGene
In all seriousness, I suspect that conditions associated with each gene are growing - we are in a phase of understanding of gene pleiotropy
May 27, 2025 at 7:23 AM
Kym Boycott #ESHG2025
Disease-Gene discoveries are falling 😲
Don't tell @DiseaseGenes bot! 🤖
#MorbidGene
In all seriousness, I suspect that conditions associated with each gene are growing - we are in a phase of understanding of gene pleiotropy
Disease-Gene discoveries are falling 😲
Don't tell @DiseaseGenes bot! 🤖
#MorbidGene
In all seriousness, I suspect that conditions associated with each gene are growing - we are in a phase of understanding of gene pleiotropy
Kym Boycott #ESHG2025
What is matchmaking
One? Two? Zero? sided
Why do we do it (see the photo below ☺️)
👍👍@deciphergenomics.bsky.social second largest contributor to MatchMaker Exchange
❓sadly, 94% of genematcher entries have no phenotype DECIPHER is much better
What is matchmaking
One? Two? Zero? sided
Why do we do it (see the photo below ☺️)
👍👍@deciphergenomics.bsky.social second largest contributor to MatchMaker Exchange
❓sadly, 94% of genematcher entries have no phenotype DECIPHER is much better
May 27, 2025 at 7:17 AM
Kym Boycott #ESHG2025
What is matchmaking
One? Two? Zero? sided
Why do we do it (see the photo below ☺️)
👍👍@deciphergenomics.bsky.social second largest contributor to MatchMaker Exchange
❓sadly, 94% of genematcher entries have no phenotype DECIPHER is much better
What is matchmaking
One? Two? Zero? sided
Why do we do it (see the photo below ☺️)
👍👍@deciphergenomics.bsky.social second largest contributor to MatchMaker Exchange
❓sadly, 94% of genematcher entries have no phenotype DECIPHER is much better
Mirjam Plantinga #ESHG2025
Ethical, Legal and Social Implications of reanalysis - a review
❓What does reanalysis mean? (See slide)
Differentiate
- Reanalysis, Reinterpretation, Reclassification
Reanalysis of what?
Cost effective?
Ethical, Legal and Social Implications of reanalysis - a review
❓What does reanalysis mean? (See slide)
Differentiate
- Reanalysis, Reinterpretation, Reclassification
Reanalysis of what?
Cost effective?
May 26, 2025 at 3:58 PM
Mirjam Plantinga #ESHG2025
Ethical, Legal and Social Implications of reanalysis - a review
❓What does reanalysis mean? (See slide)
Differentiate
- Reanalysis, Reinterpretation, Reclassification
Reanalysis of what?
Cost effective?
Ethical, Legal and Social Implications of reanalysis - a review
❓What does reanalysis mean? (See slide)
Differentiate
- Reanalysis, Reinterpretation, Reclassification
Reanalysis of what?
Cost effective?
Zornitza Stark
@zornitza.bsky.social
#ESGH2025
🤖 TALOS automatically and iteratively re-reviews genomes and exomes (including CNVs/SV on historic data)
focus on specificity - only 0.7 candidates /trio
Diagnostic yield is 5%, 248/4,744
- higher in older cases 9% 2019 4% 2022
@zornitza.bsky.social
#ESGH2025
🤖 TALOS automatically and iteratively re-reviews genomes and exomes (including CNVs/SV on historic data)
focus on specificity - only 0.7 candidates /trio
Diagnostic yield is 5%, 248/4,744
- higher in older cases 9% 2019 4% 2022
May 26, 2025 at 3:45 PM
Zornitza Stark
@zornitza.bsky.social
#ESGH2025
🤖 TALOS automatically and iteratively re-reviews genomes and exomes (including CNVs/SV on historic data)
focus on specificity - only 0.7 candidates /trio
Diagnostic yield is 5%, 248/4,744
- higher in older cases 9% 2019 4% 2022
@zornitza.bsky.social
#ESGH2025
🤖 TALOS automatically and iteratively re-reviews genomes and exomes (including CNVs/SV on historic data)
focus on specificity - only 0.7 candidates /trio
Diagnostic yield is 5%, 248/4,744
- higher in older cases 9% 2019 4% 2022
Nicola Whiffin @nickywhiffin.bsky.social #ESHG2025
Saturation genome editing of RNU4-2 reveals distinct dominant and recessive neurodevelopmental disorders
Saturation mutagenesis outperforms CADD
Novel *AR* NDD with neuroradiological features (below) - ~30 families #MorbidGene
Saturation genome editing of RNU4-2 reveals distinct dominant and recessive neurodevelopmental disorders
Saturation mutagenesis outperforms CADD
Novel *AR* NDD with neuroradiological features (below) - ~30 families #MorbidGene
May 26, 2025 at 9:45 AM
Nicola Whiffin @nickywhiffin.bsky.social #ESHG2025
Saturation genome editing of RNU4-2 reveals distinct dominant and recessive neurodevelopmental disorders
Saturation mutagenesis outperforms CADD
Novel *AR* NDD with neuroradiological features (below) - ~30 families #MorbidGene
Saturation genome editing of RNU4-2 reveals distinct dominant and recessive neurodevelopmental disorders
Saturation mutagenesis outperforms CADD
Novel *AR* NDD with neuroradiological features (below) - ~30 families #MorbidGene
Kartik Chundru (Exeter) @Chundru.bsky.social
Comprehensive characterisation of non-coding and coding effects of de novo mutations in a large-scale rare disease case-control cohort
Trios from GEL, UKB & AllOfUs
Highlight RNU non coding variants & splice site
#ESHG2025
Comprehensive characterisation of non-coding and coding effects of de novo mutations in a large-scale rare disease case-control cohort
Trios from GEL, UKB & AllOfUs
Highlight RNU non coding variants & splice site
#ESHG2025
May 26, 2025 at 9:37 AM
Kartik Chundru (Exeter) @Chundru.bsky.social
Comprehensive characterisation of non-coding and coding effects of de novo mutations in a large-scale rare disease case-control cohort
Trios from GEL, UKB & AllOfUs
Highlight RNU non coding variants & splice site
#ESHG2025
Comprehensive characterisation of non-coding and coding effects of de novo mutations in a large-scale rare disease case-control cohort
Trios from GEL, UKB & AllOfUs
Highlight RNU non coding variants & splice site
#ESHG2025
Looking for a workshop at 14:15? #ESHG2025
Since you're currently reading this, how about...
"Has social media broken scientific knowledge sharing?"
- subject experts, lively debate, audience engagement
📍 Sequencing Square (↗️ turn right as you enter exhhibitor hall)
Since you're currently reading this, how about...
"Has social media broken scientific knowledge sharing?"
- subject experts, lively debate, audience engagement
📍 Sequencing Square (↗️ turn right as you enter exhhibitor hall)
May 26, 2025 at 9:28 AM
Looking for a workshop at 14:15? #ESHG2025
Since you're currently reading this, how about...
"Has social media broken scientific knowledge sharing?"
- subject experts, lively debate, audience engagement
📍 Sequencing Square (↗️ turn right as you enter exhhibitor hall)
Since you're currently reading this, how about...
"Has social media broken scientific knowledge sharing?"
- subject experts, lively debate, audience engagement
📍 Sequencing Square (↗️ turn right as you enter exhhibitor hall)
Sébastien Küry #ESHG2025
Unveiling the crucial neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies
Unveiling the crucial neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies
May 26, 2025 at 9:06 AM
Sébastien Küry #ESHG2025
Unveiling the crucial neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies
Unveiling the crucial neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies
Rob Harkness #ESHG2025
Genetic risk of acute-onset axonal neuropathy following infection
RCC1 is novel AR #DiseaseGene
Onset ~18m #GuillianBarre-like
Clinical course #ALS-like
Proteins reduced thermal stability
🪰 reduced survival to paraquat stress
papers.ssrn.com/sol3/papers....
Genetic risk of acute-onset axonal neuropathy following infection
RCC1 is novel AR #DiseaseGene
Onset ~18m #GuillianBarre-like
Clinical course #ALS-like
Proteins reduced thermal stability
🪰 reduced survival to paraquat stress
papers.ssrn.com/sol3/papers....
May 26, 2025 at 8:58 AM
Rob Harkness #ESHG2025
Genetic risk of acute-onset axonal neuropathy following infection
RCC1 is novel AR #DiseaseGene
Onset ~18m #GuillianBarre-like
Clinical course #ALS-like
Proteins reduced thermal stability
🪰 reduced survival to paraquat stress
papers.ssrn.com/sol3/papers....
Genetic risk of acute-onset axonal neuropathy following infection
RCC1 is novel AR #DiseaseGene
Onset ~18m #GuillianBarre-like
Clinical course #ALS-like
Proteins reduced thermal stability
🪰 reduced survival to paraquat stress
papers.ssrn.com/sol3/papers....
⛓️💥Late breaking abstracts - always a great session - Space 3 #ESHG2025
Zohreh Fattahi
A new role of the deubiquitinase CYLD for mitochondrial function and integrity- promising therapeutic impact for the treatment of neurodegenerative diseases
Zohreh Fattahi
A new role of the deubiquitinase CYLD for mitochondrial function and integrity- promising therapeutic impact for the treatment of neurodegenerative diseases
May 26, 2025 at 8:45 AM
⛓️💥Late breaking abstracts - always a great session - Space 3 #ESHG2025
Zohreh Fattahi
A new role of the deubiquitinase CYLD for mitochondrial function and integrity- promising therapeutic impact for the treatment of neurodegenerative diseases
Zohreh Fattahi
A new role of the deubiquitinase CYLD for mitochondrial function and integrity- promising therapeutic impact for the treatment of neurodegenerative diseases
@zornitza.bsky.social opening a well-attended Newborn Screening session with a talk on choosing conditions
Subjectivity in application of widely agreed inclusion criteria leads to small overlap (55 genes)
pubmed.ncbi.nlm.nih.gov/38275146/
Subjectivity in application of widely agreed inclusion criteria leads to small overlap (55 genes)
pubmed.ncbi.nlm.nih.gov/38275146/
May 26, 2025 at 6:43 AM
@zornitza.bsky.social opening a well-attended Newborn Screening session with a talk on choosing conditions
Subjectivity in application of widely agreed inclusion criteria leads to small overlap (55 genes)
pubmed.ncbi.nlm.nih.gov/38275146/
Subjectivity in application of widely agreed inclusion criteria leads to small overlap (55 genes)
pubmed.ncbi.nlm.nih.gov/38275146/
Looking for a poster?
Have a look at P14 002.B and then message me! I would love to discuss!
🧠 New degenerative neurological condition
4️⃣ Caused by a triplication on 16p
🔁 Mediated by a palindromic repeat
#ESHG2025
Have a look at P14 002.B and then message me! I would love to discuss!
🧠 New degenerative neurological condition
4️⃣ Caused by a triplication on 16p
🔁 Mediated by a palindromic repeat
#ESHG2025
May 25, 2025 at 3:53 PM
Looking for a poster?
Have a look at P14 002.B and then message me! I would love to discuss!
🧠 New degenerative neurological condition
4️⃣ Caused by a triplication on 16p
🔁 Mediated by a palindromic repeat
#ESHG2025
Have a look at P14 002.B and then message me! I would love to discuss!
🧠 New degenerative neurological condition
4️⃣ Caused by a triplication on 16p
🔁 Mediated by a palindromic repeat
#ESHG2025
Siddharth Banka #ESHG2025
R-loop forming regions genes #RNU2-2 and #RNU5B-1 novel non-coding NDD genes #MorbidGene
Clinical features of these new "RNU"pathies
- Hypotonia, macrocephaly, seizures, FTT
- explain 10-15 / 1000 rare NDDs
www.medrxiv.org/content/10.1...
R-loop forming regions genes #RNU2-2 and #RNU5B-1 novel non-coding NDD genes #MorbidGene
Clinical features of these new "RNU"pathies
- Hypotonia, macrocephaly, seizures, FTT
- explain 10-15 / 1000 rare NDDs
www.medrxiv.org/content/10.1...
May 25, 2025 at 9:49 AM
Siddharth Banka #ESHG2025
R-loop forming regions genes #RNU2-2 and #RNU5B-1 novel non-coding NDD genes #MorbidGene
Clinical features of these new "RNU"pathies
- Hypotonia, macrocephaly, seizures, FTT
- explain 10-15 / 1000 rare NDDs
www.medrxiv.org/content/10.1...
R-loop forming regions genes #RNU2-2 and #RNU5B-1 novel non-coding NDD genes #MorbidGene
Clinical features of these new "RNU"pathies
- Hypotonia, macrocephaly, seizures, FTT
- explain 10-15 / 1000 rare NDDs
www.medrxiv.org/content/10.1...