Description
Pulmonary arterial hypertension inclusion criteria eligibility statement.

Pulmonary arterial hypertension inclusion criteria :
Unexplained pulmonary arterial hypertension (PAH) or pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis*
The diagnosis of PAH/PVOD is defined by the presence of pre-capillary pulmonary hypertension. This is established at the time of right heart catheterisation by an increase in mean pulmonary arterial pressure (PAPm) greater then 25 mmHg at rest, by a pulmonary artery wedge pressure (PAWP) less than15 mmHg and a pulmonary vascular resistance (PVR) greater than 3 Wood units (WU) in the absence of other causes of pre-capillary pulmonary hypertension, such as that due to lung diseases, embolic disease, or other rare diseases (see exclusion criteria).

Pulmonary arterial hypertension exclusion criteria :
Left heart disease; Lung disease/hypoxaemia; other disease with likely causative role (including myeloproliferative disorders, sarcoidosis, vasculitis, NF1, HIV, sickle cell disease)

Prior genetic testing guidance :
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Pulmonary arterial hypertension prior genetic testing genes :
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
BMPR2, ACVRL1 (ALK1), ENG, SMAD9

Closing statement :
These requirements will be kept under continual review during the main programme and may be subject to change.

This panel includes genes and from BRIDGE consortium Tier 1 genes from NIHR BioResource – Rare Diseases Study (NIHRBR-RD) sent by Dr Karyn Megy, WGS Clinical Feedback Lead and incorporates pertinent genes associated to PAH.
The following experts from the BRIDGE consortium NIHRBR-RD contributed : 
Professor Nicolas Morrell (Cambridge University Hospitals NHS Foundation Trust), Dr Simon Holden (Cambridge University Hospitals NHS Foundation Trust), Dr Stefan Graf (NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust), Dr Charaka Hadinnapola (Papworth Hospital NHS Foundation Trust), Louise Daugherty (NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust), Dr Karyn Megy (NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust), Rutendo Mapeta (NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust)

4 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

  • BRIDGE consortium (NIHRBR-RD)

    Group: Other
    Workplace: Other

  • Arianna Tucci (Genomics England Curator)

    Group: Other
    Workplace: Other

17 Entities

17 reviewed, 10 green

List Entity Reviews Mode of inheritance Details
17 Entitiess
Green Green List (high evidence)
ACVRL1
2 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
  • Literature
  • UKGTN
Phenotypes
  • Telangiectasia, hereditary hemorrhagic, type 2, 600376
  • Heritable pulmonary arterial hypertension
  • HPAH
Tags
Green Green List (high evidence)
ATP13A3
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Heritable pulmonary arterial hypertension
  • HPAH
Tags
Green Green List (high evidence)
BMPR2
3 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Pulmonary hypertension, familial primary, 1, with or without HHT, 178600
  • Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associated, 178600
  • Idiopathic pulmonary arterial hypertension
  • IPAH
  • Heritable pulmonary arterial hypertension
  • HPAH
  • Pulmonary arterial hypertension
  • Pulmonary venoocclusive disease 1, 265450
  • PVOD
Tags
Green Green List (high evidence)
EIF2AK4
2 reviews
2 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert list
  • Literature
Phenotypes
  • Pulmonary venoocclusive disease 2, 234810
  • PVOD
  • pulmonary capillary hemangiomatosis
  • PCH
  • Heritable pulmonary arterial hypertension
  • HPAH
  • Pulmonary arterial hypertension
  • Idiopathic pulmonary arterial hypertension
  • IPAH
Tags
Green Green List (high evidence)
ENG
2 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Telangiectasia, hereditary hemorrhagic, type 1, 187300
  • Heritable pulmonary arterial hypertension
  • HPAH
  • Hereditary hemorrhagic telangiectasia
  • HHT
Tags
Green Green List (high evidence)
GDF2
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Heritable pulmonary arterial hypertension
  • HPAH
Tags
Green Green List (high evidence)
KCNK3
3 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Expert list
  • Literature
Phenotypes
  • Idiopathic pulmonary arterial hypertension
  • IPAH
  • Heritable pulmonary arterial hypertension
  • HPAH
  • Pulmonary arterial hypertension
  • Pulmonary hypertension, primary, 4, 615344
Tags
Green Green List (high evidence)
SMAD9
2 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Idiopathic pulmonary arterial hypertension
  • IPAH
  • Heritable pulmonary arterial hypertension
  • HPAH
  • Pulmonary arterial hypertension
  • Pulmonary hypertension, primary, 2, 615342
Tags
Green Green List (high evidence)
SOX17
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Heritable pulmonary arterial hypertension
  • HPAH
Tags
Green Green List (high evidence)
TBX4
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Ischiocoxopodopatellar syndrome, 147891
  • Small patella syndrome
  • SPS
  • Idiopathic pulmonary arterial hypertension
  • IPAH
  • Heritable pulmonary arterial hypertension
  • HPAH
  • Pulmonary arterial hypertension
Tags
Amber Amber List (moderate evidence)
AQP1
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Heritable pulmonary arterial hypertension
  • HPAH
Tags
Amber Amber List (moderate evidence)
CAV1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Emory Genetics Laboratory
  • Expert Review Amber
  • Expert list
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Pulmonary hypertension, primary, 3, 615343
  • Heritable pulmonary arterial hypertension
  • HPAH
  • Pulmonary arterial hypertension
Tags
Red Red List (low evidence)
BMPR1B
1 review
Unknown
Sources
  • Expert Review Red
  • Literature
Phenotypes
  • Idiopathic pulmonary arterial hypertension
  • IPAH
Tags
Red Red List (low evidence)
CBLN2
1 review
1 red
Unknown
Sources
  • Literature
Tags
Red Red List (low evidence)
KCNA5
1 review
1 red
Unknown
Sources
  • Literature
Phenotypes
  • Idiopathic pulmonary arterial hypertension
  • IPAH
Tags
Red Red List (low evidence)
SMAD1
2 reviews
1 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert list
  • Literature
Phenotypes
  • Idiopathic pulmonary arterial hypertension
  • IPAH
  • heritable pulmonary arterial hypertension
  • HPAH
Tags
Red Red List (low evidence)
SMAD4
2 reviews
1 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert list
  • Literature
Phenotypes
  • Idiopathic pulmonary arterial hypertension
  • IPAH
  • Heritable pulmonary arterial hypertension
  • HPAH
  • Pulmonary arterial hypertension
  • Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050
Tags

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