Description
Familial Thoracic Aortic Aneurysm Disease (11021) Eligibility statement:

Relevant Diseases:
- Familial Thoracic Aortic Aneurysm and dissection 
- Thoracic aortopathy < 50 years with no other established risk factors 
- Clinically diagnosed Marfan syndrome with no FBN1 mutation 
- Loeys-Dietz syndrome and Loeys-Dietz syndrome like conditions 
- Mutation negative Congenital Contractural Arachnodactyly (Beals syndrome)

Familial Thoracic Aortic Aneurysm Disease inclusion criteria (Conditions) (29317)
- patients suspected to have the above conditions
Individuals with severe or syndromic disease should be recruited according to standard guidance, typically as trios. Disease status of apparently unaffected participants should be determined according to standard clinical practice to detect cryptic disease.  In other cases, unaffected individuals should not be recruited. Recruitment in such families should favour multiplex families over single isolated cases. These singleton recruits will not contribute to the overall singleton monitoring metrics applied to GMCs.

Familial Thoracic Aortic Aneurysm Disease exclusion criteria: (29317)
- Sporadic thoracic aortopathies with risk factors
- Family history with no affected proband to test

Prior genetic testing guidance (29317)
- 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.

Familial Thoracic Aortic Aneurysm Disease prior genetic testing genes: (29317)

Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 - Loeys-Dietz syndrome TGFBR1 and TGFBR2
 - Marfan Syndrome FBN1
 - Congenital Contractural Arachnodactyly FBN2
 - Isolated familial thoracic aortic aneurysms and dissection - ACTA2

Closing statement (29317)
These requirements will be kept under continual review during the main programme and may be subject to change.

10 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Bill Newman (Manchester Centre for Genomic Medicine)

    Group: other
    Workplace: other

  • Helen Savage (Congenica Ltd)

    Group: Other biotech or pharmaceutical
    Workplace: Other clinical service

  • Matina Prapa (Genomics England Curator)

    Group: GeCIP domain
    Workplace: Other

  • Nick Camm (NHS)

    Group: Other NHS organisation
    Workplace: NHS diagnostic lab

  • David Parry (University of Edinburgh)

    Group: GeCIP domain
    Workplace: Research lab

  • Caroline Wright (Genomics England Curator)

    Group: Other
    Workplace: Genomics England

  • Rebecca Foulger (Genomics England curator)

    Group: Other
    Workplace: Other

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Helen Brittain (Genomics England Curator)

    Group: Other
    Workplace: Other

57 Entities

57 reviewed, 29 green

List Entity Reviews Mode of inheritance Details
57 Entitiess
Green Green List (high evidence)
ACTA2
3 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Thoracic aortic aneurysm and dissection
  • Aortic aneurysm, familial thoracic 6, 611788
  • Multisystemic smooth muscle dysfunction syndrome, 613834
  • Moyamoya disease 5, 614042
  • Thoracic Aortic Aneurysms and Aortic Dissections
  • Isolated familial thoracic aortic aneurysms and dissection
Tags
Green Green List (high evidence)
BGN
1 review
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • Other
Phenotypes
  • syndromic thoracic aortic aneurysm and dissection
  • X-linked syndromic TAAD
Tags
Green Green List (high evidence)
COL1A1
5 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert list
Phenotypes
  • Ehlers-Danlos syndrome, classic, 130000
  • Ehlers-Danlos syndrome, type VIIA, 130060
Tags
Green Green List (high evidence)
COL1A2
5 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert list
Phenotypes
  • Ehlers-Danlos syndrome, cardiac valvular form
  • Ehlers-Danlos syndrome, type VIIB
Tags
Green Green List (high evidence)
COL3A1
3 reviews
2 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
  • UKGTN
Phenotypes
  • Loeys-Dietz syndrome
  • Ehlers-Danlos syndrome, type IV, 130050
Tags
Green Green List (high evidence)
COL5A1
5 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
Phenotypes
  • Ehlers-Danlos syndrome vascular type
  • Ehlers-Danlos syndrome, classic type, 130000
Tags
Green Green List (high evidence)
COL5A2
5 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
Phenotypes
  • multisystemic smooth muscle dysfunction syndrome
  • Ehlers-Danlos syndrome, classic type, 130000
Tags
Green Green List (high evidence)
EFEMP2
4 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert list
Phenotypes
  • Cutis laxa, autosomal recessive, type IB, 614437
  • aortic aneurysm
Tags
Green Green List (high evidence)
ELN
4 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert list
Phenotypes
  • Cutis laxa, autosomal dominant, 123700
  • Supravalvar aortic stenosis, 185500
Tags
Green Green List (high evidence)
FBN1
4 reviews
3 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Aortic aneurysm, ascending, and dissection
  • ongenital contracturalarachnodactyly
  • Marfan Syndrome
Tags
Green Green List (high evidence)
FBN2
4 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Contractural arachnodactyly, congenital, 121050
  • Congenital Contractural Arachnodactyly
Tags
Green Green List (high evidence)
FLCN
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
Phenotypes
  • Pneumothorax, primary spontaneous, 173600
  • Birt-Hogg-Dube syndrome,135150
Tags
Green Green List (high evidence)
FLNA
4 reviews
2 green
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
Phenotypes
  • Marfan Syndrome, Thoracic Aortic Aneurysm & Dissection (TAAD), and Related Disorders
Tags
Green Green List (high evidence)
LOX
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • aortic aneurysm
  • Aortic aneurysm, familial thoracic 10, 617168
Tags
Green Green List (high evidence)
MED12
5 reviews
2 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
Phenotypes
  • Lujan-Fryns syndrome, 309520
  • Marfan Syndrome, Thoracic Aortic Aneurysm & Dissection (TAAD), and Related Disorders
Tags
Green Green List (high evidence)
MYH11
4 reviews
3 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Aortic aneurysm, familial thoracic 4, 132900
Tags
Green Green List (high evidence)
MYLK
3 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Aortic aneurysm, familial thoracic 7, 613780
Tags
Green Green List (high evidence)
NOTCH1
5 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
Phenotypes
  • Aortic valve disease 1, 109730
Tags
Green Green List (high evidence)
PLOD1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Ehlers-Danlos syndrome, type VI, 225400
  • kyphoscoliotic EDS
Tags
Green Green List (high evidence)
PRKG1
3 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Aortic aneurysm, familial thoracic 8, 615436
Tags
Green Green List (high evidence)
SKI
3 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
Phenotypes
  • Marfan Syndrome, Thoracic Aortic Aneurysm & Dissection (TAAD), and Related Disorders
  • Shprintzen-Goldberg Craniosynostosis Syndrome, 182212
  • Shprintzen-Goldberg Craniosynostosis Syndrome, 182212
Tags
Green Green List (high evidence)
SLC2A10
4 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
Phenotypes
  • Marfan Syndrome, Thoracic Aortic Aneurysm & Dissection (TAAD), and Related Disorders
  • Arterial tortuosity syndrome, 208050
Tags
Green Green List (high evidence)
SMAD2
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Other
Phenotypes
  • arterial aneurysms and dissections
Tags
  • watchlist
Green Green List (high evidence)
SMAD3
3 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Loeys Dietz syndrome, type 3, 613795
Tags
Green Green List (high evidence)
SMAD4
3 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert list
Phenotypes
  • Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050
Tags
Green Green List (high evidence)
TGFB2
5 reviews
3 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Loeys-Dietz syndrome 4, 614816
Tags
Green Green List (high evidence)
TGFB3
5 reviews
1 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Loeys-Dietz syndrome 5, 615582
  • Arrhythmogenic right ventricular dysplasia 1, 107970
Tags
Green Green List (high evidence)
TGFBR1
3 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Loeys Dietz syndrome, type 1A, 609192
  • Loeys Dietz syndrome, type 2A, 608967
  • Loeys-Dietz syndrome
Tags
Green Green List (high evidence)
TGFBR2
4 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert Review Green
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Loeys Dietz syndrome, type 1B, 610168
  • Loeys Dietz syndrome, type 2B, 610380
  • Loeys-Dietz syndrome
Tags
Amber Amber List (moderate evidence)
PKD1
1 review
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Polycystic kidney disease, adult type I,173900
  • Connective Tissue Disorders
Tags
Amber Amber List (moderate evidence)
PKD2
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Polycystic kidney disease 2, 613095
  • Connective Tissue Disorders
Tags
Red Red List (low evidence)
ABCC6
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
ACVR1
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
ADAMTS2
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
ALDH18A1
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
ATP6V0A2
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
ATP7A
2 reviews
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
B4GALT7
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
CBS
3 reviews
2 red
Not set
Sources
  • Emory Genetics Laboratory
  • Expert list
Phenotypes
  • Marfan syndrome
Tags
Red Red List (low evidence)
CHST14
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
COL11A1
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
COL11A2
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
COL2A1
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
COL4A1
3 reviews
2 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps
  • Angiopathy, hereditary, with nephropathy, aneurysms, and muscle, 611773
Tags
Red Red List (low evidence)
COL9A1
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
COL9A2
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
COL9A3
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
FBLN5
4 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Expert list
Tags
Red Red List (low evidence)
FKBP14
4 reviews
1 green 1 red
Not set
Sources
  • Expert Review Red
  • Expert list
Tags
Red Red List (low evidence)
FOXE3
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Literature
Phenotypes
  • {Aortic aneurysm, familial thoracic 11, susceptibility to}
Tags
Red Red List (low evidence)
HNRNPK
3 reviews
2 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Other
Tags
Red Red List (low evidence)
KCNN1
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • UKGTN
Tags
Red Red List (low evidence)
LTBP2
1 review
Unknown
Sources
  • Literature
Phenotypes
  • Marfan syndrome
Tags
Red Red List (low evidence)
MFAP5
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Other
Phenotypes
  • Aortic aneurysm, familial thoracic 9, 616166
Tags
Red Red List (low evidence)
SLC39A13
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
TNXB
2 reviews
1 red
Not set
Sources
  • Expert list
Tags
Red Red List (low evidence)
ZNF469
2 reviews
1 red
Not set
Sources
  • Expert list
Tags

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