Join Mailing List   |   Jobs   |   Print Page   |   Contact Us   |   Sign In   |   Join
2016 Annual Minutes
Thread Score:
Page 1 of 1
Thread Actions

6/28/2016 at 8:15:57 PM GMT
Posts: 3
2016 Annual Minutes

ISTH-SSC 2016 Meeting Montpellier May 25-28

SSC Genomics in Thrombosis and Hemostasis (SSC GinTH)


Room Rondelet, Friday 27th May 2016, 14:15-18:45,



Professor Willem H Ouwehand (United Kingdom)


Dr Daniel Bellissimo (United States) - absent

Professor Paul Bray (United States) - absent

Professor Kathleen Freson (Belgium) - present

Professor Anne Goodeve (United Kingdom) - present

Dr Michele P Lambert (United States) - present




Speaker: Jose Maria Bastida (Spain).

Title: Design and Application of a twenty-three-gene panel by NGS for inherited coagulation bleeding disorder.

The results of the panel test were presented based on a national initiative across Spain with many examples of multiple cases per rare disease type.  It illustrated how national collaboration in the field of Next Gen Seq can quickly deliver benefits for patients and their close relatives.


Session 1

Moderator: Professor Willem H Ouwehand (United Kingdom)


Welcome by Professor Willem H Ouwehand

Professor Willem H Ouwehand presented an overview of the SSC Genomics in Thrombosis and Haemostasis.


Title: ThromboGenomics High Throughput Sequencing Platform.

Speaker: Kate Downes (Cambridge, UK)

Question about coverage

– >costs of sequencing become less important – MDT members time is more costly

Question about Sanger confirmation

-> Willem Ouwehand pointed out that this is likely to become more redundant/cost inefficient and likely that after the ISTH Conference in Berlin (2017) we decide not to do it anymore for simple variants.  More complex variants may require confirmation by Sanger sequencing.

Question  - new genes do they cause specific diseases – [3 of these just say thrombo/macrothrombocytopenica]

-> Kathleen Freson pointed out these were multi-tissue disorders – e.g. DIAPH1 gain-of-function resulting in macrothrombocytopenia and deafness

Question  – Transcription Factor genes (e.g. RUNX1, ETV6, etc) and the increased risk of cancer – there needs to be clear policy on difference between research and routine clinical service

-> the Odds Ratio (OR) needs to be more precisely defined

-> calculating OR values is only possible if we aggregate cases across countries

-> decisions on introduction of ‘predictive testing’ need to consider national policies and guidelines

-> the principle of ‘autonomy’ should be a key driver in setting policies - several people argued that our obligation as professionals is to provide ‘information in an objective and evidence based manner’ and inform the public about the pro’s and con’s of genetic tests

-> the principle of autonomy needs to replace the ‘paternalistic’ approach of ‘doctor knows best’


Title: Statistical challenges of identifying the genetic determinant of rare diseases.

Speaker: Ernest Turro  (UK)

Question: How do we tell whether variants in the non-coding space are disease causing?

–> The statistical principals for identifying putative causal rare variants were reviewed

Comment: phenotypes may change over time (e.g. in MYH9-related disorders) and it is therefore important to capture changes in phenotype with progressing age

-> New statistical methods are required to use the data richness (OMIM, MPO, HPO, etc) to assign likelihoods to genes and variants therein of being causal of rare disease


Session 2

Moderator: Andres Greinacher (Germany)


Title: Assigning pathogenicity status to DNA variants

Speaker: Kathleen Freson (Belgium)

Kathleen Fresson reported on the European and US guidelines for reporting variants:

-          “variant” is the word to use, not “mutations” or “polymorphisms”

-          VUS must not be included in clinical reports,

-          VUS can be included in research report to draw the attention of clinician-scientists to certain variants which require further study (e.g. co-segregation, functional genomics studies, etc. 

-          conservative reporting on the status of variants as ‘likely pathogenic variant’ and ‘pathogenic variant’ (LPV and PV, respectively) should be the mantra

Question: Policy paper on variant/mutation/polymorphisms

Willem H Ouwehand (WHO):

-          The American Society for Hematology (ASH) has started a Precision Medicine task force providing a forum to set policies on high-penetrance germline variants and somatic mutations; policies and guidelines will be developed over the next 24 months with short manuscripts in Blood.

-          There will be an informal discussion at the EHA-Copenhagen meeting on having a similar cross-cutting Scientific Working Group for the EHA


Title: Reference Variant Databases

Speaker: Karyn Mégy (UK) and Muriel Giansily-Blaizot (France)

Presentations dealt with the need for consistence use of a frame of reference for the consistent annotation of variants; Databases like LRG, ClinVar and EAHAD were reviewed and a in-depth review of F7 variants and their clinical consequences.

Question: What about variants in other loci that modify the severity of phenotype; identifying such modifiers requires large datasets on thousands of patients?

The application of genome-wide typing in combination with HTS panel tests may provide an approach to identify ‘strong modifiers’ in the future. 


Session 3

Moderator: Andreas Greinacher (Germany)


Title: Regulation of haemostasis by miRNAs: implication for thrombus formation

Speaker: Martinez Gomez (Spain)

This talk provided a comprehensive and authoritative overview over the role of miRNA’s in platelet biology. 

Question: Are there examples of rare inherited platelet diseases which are caused by variants in the miRNA genes or miRNA binding sites

-> Dicer knockout in mice does alter platelet proteomics


Title: Differential diagnosis of congenital macrothrombocytopenia

Speaker: Shinji Kunishima (Japan)

The presentation reviewed the current state of knowledge on macrothrombocytopenia with a focus on ACTN1

Title: Reprogramming of platelet miRNA induced by activation

Speaker: Giovanni Cimmino (Italy)

Question – How long after activation do you see difference in mRNA expression

-> time course up to 2 hour

Question –do miRNAs influence thrombus formation?

-> possibly miRNAs act early in activation


Session 4

Moderator: Kathleen Freson (Belgium)


Title: Common gene variation affecting platelet function

Speaker: Leonard Edelstein (United States)

Leonard gave an excellent talk about genome wide association studies for platelet function and the role of expression-QTLs at GWAS associated regions as the underlying mechanism.  Several eQTL datasets have now been produced and it would be interesting to investigate the possibility of merging data to create a ‘truth set’

Question – about ethnicity

è Could it be that admixture may have explained the observed associations between variants and platelet function

è Ethnicity was being included in the analysis using the genome-wide types to cluster cases of different ethnicity.


Title: Phenotyping and genotyping of inherited platelet disorders: experience from a Spanish National Project.

Speaker: Jose Rivera Pozo (Spain)

Questions – how many Glanzmann cases have been identified?

-> tens of cases and most cases have their own causal variants


General discussion

Anne Goodeve (UK) advertised a workshop:

ISTH Advanced Training Course in Thrombosis and Haemostatis.

Location: St Anne’s College, Oxford, England, UK.

Dates: Sept. 6th -9th, 2016.


Kate Downes proposed to include four new genes to the Tier 1 list:

-          CHST14

-          DIAPH1

-          MECOM (previously EVI1)

-          TUBB1 

This was accepted by the membership


Karyn Mégy advised that:

(1)   LPV and PV should be submitted to the ClinVar database

(2)   Tier 1 genes and the clinically relevant transcript(s) must be registered with the Locus Reference Genomics database.

(3)   Richer annotation of variants has been achieved through Locus Specific Databases, e.g. EAHAD for F7, F8, F9 and VWF, Glanzmann Thrombasthenia, …..


Andreas Greinacher did bring up the issue of rare variants in transcription factor genes implicated in bleeding and platelet disorders that may enhance the risk of malignancies (e.g. RUNX1, ETV6, WAS).


Comments from SSC membership:

-          This needs to be a debate for the public. In the UK this is starting to happen….. and is widely supported by the media

-          We should respect the principle of autonomy; we need to inform patients and their close relatives and offer choice

-          If a patient consent to a genetic test they need to be informed upfront that they may receive results about increased risks for malignancies, deafness, kidney insufficiency, etc.


Panel discussion: sharing genotype and phenotype data in inherited disorders.


  •  Introduction of a Green Paper about adopting a practice of sharing of data on genotype and phenotype.  Fort Lauderdale Agreement[1]: make sequence data available as early as possible.

o   Genome sequence data generated across Europe are submitted to the European Genome-phenome Archive (EGA)

  • The Green Paper discussion document will be distributed to the SSC membership using the services provided by the SSC office
  • The membership of the SSC is to be consulted on the content of the Green Paper with the aim to develop a White Paper for ratification at the ISTH meeting Berlin 2017
  • The White Paper would inform the working of the ISTH-SSC for Genomics in Thrombosis and Haemostasis (SSC-GinTH)



  • Attendees to the meeting should register as Member of the SSC-GinTH at
  • Green Paper will be circulated via ISTH-SSC website


Andreas Greinacher:

  • Sharing OK, but at which time point, which type of data?
  • Between data and publishing paper can take 2 years … share straight away, or when abstract submitted, or when paper accepted?



  • in UK we have 6-months (100 000 Genomes Project) or 12-months timeline (NIHR BioResource – Rare Diseases, Deciphering Developmental Disorders project) for genotype and phenotype data release;
  • these timelines are contractually stipulated by the fund providers. Sharing data early should be the mantra, but everyone recognises that ‘researchers need their manuscripts to enhance their chances for future funding





  • Instead of publishing manuscripts reporting on a couple of patients by several groups, we may want to consider to have manuscripts with many cases per gene (see Green Paper)
  • About half of the audience agreed with that, the rest had no opinion or was not that much in favour of early data sharing
  • It was pointed out that those that were not in support of data sharing may not be attending the meeting


Writing committee for genes


Maha Othman: writing committee: who does what, who’s authoring etc. Is it a fixed formula? Is that decided by the writing committee for a certain paper?


Self-organisation of the Writing Committee but WHO suggested that they should: 

1. multi-disciplinary

2. include early career researchers

3. small committee membership (cannot write a paper with 25 people)

4. requirement for experts in bioinformatics and statistical genomics


The following manuscripts which would make use of the ThromboGenomics HTS results were discussed:


Rémi Favier has offered to lead on the writing of a manuscript about ~35 Grey Platelet Syndrome (GPS) cases – anyone who wants to include GPS cases should contact Remi Favier at or Tadbir Bariana at


Paolo Gresele has expressed an interest to lead on the writing about the aggregated MYH9 cases – those who want to contribute should contact Prof Paolo Gresele at


Andreas Greinacherthere is a study on the use of manganese in MYH9 patients. Anyone who can contribute cases please contact Andreas Greinacher at We do not want multiple underpowered observational studies – so let’s join forces in the interest of patients


WHO: Offered to collate all new LPV and PVs in the Tier 1 genes (see Green Paper), and do a single upload to ClinVar once a year on behalf of the SSC-GinTH (see Green Paper). Interested parties are to contact Karyn Megy at


There was wide support for the above proposed manuscripts and attendees who want to contribute to a Writing Committee should email the lead author.


What about intellectual property



  • The vast majority of research on Rare Diseases is pre-competitive in nature.
  • The Supreme Court of America has ruled that the relation between germline variants and phenotype cannot be patented


European Genome-phenome Archive (EGA)[2]

WHO introduced EGA: Sequences and variants and phenotypes information can be submitted to the EGA – access is regulated by a Data Access Committee (i.e. SSC Chair and Co-Chairs would oversee access to data until publication).

Question: Kathleen Freson

Sequences are available via EGA, but how much phenotype is given?

WHO: phenotype, detailed enough to be useful, but not too much that would allowed to identify the patient, e.g. higher level leaves of HPO tree.

The equivalent in the US is dbGaP[3]. dbGaP and EGA exchange metadata information, not sequence files.

The presentations are available as pdf files at the following link:


Willem H Ouwehand, Cambridge, UK

June 2016

Membership Management Software Powered by YourMembership  ::  Legal
This website uses cookies to store information on your computer. Some of these cookies are used for visitor analysis, others are essential to making our site function properly and improve the user experience. By using this site, you consent to the placement of these cookies. Click Accept to consent and dismiss this message or Deny to leave this website. Read our Privacy Statement for more.