List of diseases covered by Ehlers-Danlos Syndrome NGS panel

Published 18/12/2018

List of diseases covered by
Ehlers-Danlos Syndrome NGS panel

Gene Condition
ADAMTS2 Ehlers-Danlos syndrome, dermatosparaxis type
AEBP1 Ehlers-Danlos syndrome, classic-like, 2
ALDH18A1 Cutis laxa, autosomal dominant 3;
Cutis laxa, autosomal recessive, type IIIA;
Spastic paraplegia 9A, autosomal dominant;
Spastic paraplegia 9B, autosomal recessive
ATP7A Occipital horn syndrome; Menkes disease;
Spinal muscular atrophy, distal, X-linked 3
ATP6V0A2 Cutis laxa, autosomal recessive, type IIA;
Wrinkly skin syndrome
B3GALT6 Ehlers-Danlos syndrome, spondylodysplastic type, 2;
Spondyloepimetaphyseal dysplasia with joint laxity, type 1,
with or without fractures
B3GAT3 Multiple joint dislocations, short stature,
craniofacial dysmorphism, with or without congenital heart defects
B4GALT7 Ehlers-Danlos syndrome, spondylodysplastic type, 1
CHST14 Ehlers-Danlos syndrome, musculocontractural type 1
COL12A1 Bethlem myopathy 2;
Ullrich congenital muscular dystrophy 2
COL1A1 Ehlers-Danlos syndrome, arthrochalasia type, 1;
Caffey disease; Osteogenesis imperfecta, type I;
Osteogenesis imperfecta, type II;
Osteogenesis imperfecta, type III; Osteogenesis imperfecta, type IV
COL1A2 Ehlers-Danlos syndrome, arthrochalasia type, 2;
Ehlers-Danlos syndrome, cardiac valvular type;
Osteogenesis imperfecta, type II;
Osteogenesis imperfecta, type III; Osteogenesis imperfecta, type IV
COL3A1 Ehlers-Danlos syndrome, vascular type
COL5A1 Ehlers-Danlos syndrome, classic type, 1
COL5A2 Ehlers-Danlos syndrome, classic type, 2
C1R Ehlers-Danlos syndrome, periodontal type, 1
C1S Ehlers-Danlos syndrome, periodontal type, 2;
C1s deficiency
GORAB Geroderma osteodysplasticum
DSE Ehlers-Danlos syndrome, musculocontractural type 2
EFEMP2 Cutis laxa, autosomal recessive, type IB
ELN Cutis laxa, autosomal dominant;
Supravalvar aortic stenosis
FBLN5 Cutis laxa, autosomal dominant 2;
Cutis laxa, autosomal recessive, type IA;
Neuropathy, hereditary, with or without age-related macular degeneration
FBN1 Acromicric dysplasia; Ectopia lentis, familial;
Geleophysic dysplasia 2; Marfan lipodystrophy syndrome;
Marfan syndrome;
MASS syndrome; Stiff skin syndrome;
Weill-Marchesani syndrome 2, dominant
FKBP14 Ehlers-Danlos syndrome, kyphoscoliotic type, 2
FLNA FG syndrome 2; Cardiac valvular dysplasia, X-linked;
Congenital short bowel syndrome; Frontometaphyseal dysplasia 1;
Heterotopia, periventricular; Melnick-Needles syndrome;
Otopalatodigital syndrome, type I;
Otopalatodigital syndrome, type II;
Terminal osseous dysplasia
LTBP4 Cutis laxa, autosomal recessive, type IC
PLOD1 Ehlers-Danlos syndrome, kyphoscoliotic type, 1
PRDM5 Brittle cornea syndrome 2
PYCR1 Cutis laxa, autosomal recessive, type IIB;
Cutis laxa, autosomal recessive, type IIIB
RIN2 Macrocephaly, alopecia, cutis laxa, and scoliosis
SLC39A13 Ehlers-Danlos syndrome, spondylodysplastic type, 3
SMAD2 Arterial aneurysmal disease
SMAD3 Loeys-Dietz syndrome 3
TGFB2 Loeys-Dietz syndrome 4
TGFBR1 Loeys-Dietz syndrome 1
TGFBR2 Loeys-Dietz syndrome 2;
TNXB Ehlers-Danlos syndrome, classic-like, 1
ZNF469 Brittle cornea syndrome 1

Ehlers-Danlos Syndrome NGS panel

Published 18/12/2018

Ehlers-Danlos Syndrome NGS panel

Genes
(full
coding region):		 ADAMTS2, AEBP1, ALDH18A1, ATP7A, ATP6V0A2, B3GALT6, B3GAT3, B4GALT7, CHST14, COL12A1, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, C1R, C1S, GORAB, DSE, EFEMP2, ELN, FBLN5, FBN1, FKBP14, FLNA, LTBP4, PLOD1, PRDM5, PYCR1, RIN2, SLC39A13, SMAD2, SMAD3, TGFB2, TGFBR1, TGFBR2, TNXB, ZNF469

List of diseases covered by the panel
Lab method: NGS panel with CNV analysis
TAT: 6-9 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of Ehlers-Danlos syndrome types and other genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Ehlers-Danlos syndrome (EDS) is a group of rare disorders affecting connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. The 2017 classification describes 13 types of EDS. The symptoms depend upon the specific type of EDS. An unusually large range of joint movement occurs in most forms of EDS and many individuals with the EDS have soft, velvety skin that is highly stretchy (elastic) and fragile. The vascular type of disease causes bleeding problems, the cardiac-valvular type causes severe problems with the valves that control the movement of blood through the heart, and people with the kyphoscoliotic type experience severe curvature of the spine.

The test covers the known genetic causes of EDS types and a range of other genetically/phenotypically related disorders.

Depending on the type of EDS it could be inherited in an autosomal dominant or autosomal recessive pattern.

The combined prevalence of all types of EDS is estimated to affect 1 in 2500 to 5000 individuals in the general population. Most common are hypermobile and classical forms affecting 1 in 5,000 to 20,000 people and 1 in 20,000 to 40,000 people, respectively. Other forms of EDS are extremely rare.

References:

Byers PH. Vascular Ehlers-Danlos Syndrome. 1999 Sep 2 [Updated 2019 Feb 21]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1494/
Levy HP. Ehlers-Danlos Syndrome, Hypermobility Type. 2004 Oct 22 [updated 2016 Mar 31]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1279/
Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8-26. doi:10.1002/ajmg.c.31552. PMID: 28306229
Malfait F, Wenstrup R, De Paepe A. Ehlers-Danlos Syndrome, Classic Type. 2007 May 29 [updated 2011 Aug 18]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1244/
Pepin MG, Murray ML, Byers PH. Vascular Ehlers-Danlos Syndrome. 1999 Sep 2 [updated 2015 Nov 19]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1494/
Cannaerts E, Kempers M, Maugeri A, et al. Novel pathogenic SMAD2 variants in five families with arterial aneurysm and dissection: further delineation of the phenotype. J Med Genet. 2019;56(4):220-227. doi:10.1136/jmedgenet-2018-105304. PMID: 29967133

Ehlers-Danlos Syndrome NGS panel

Published 26/09/2018

Ehlers-Danlos Syndrome NGS panel

Genes
(full
coding region):		 ADAMTS2, AEBP1, ALDH18A1, ATP7A, ATP6V0A2, B3GALT6, B3GAT3, B4GALT7, CHST14, COL12A1, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, C1R, C1S, GORAB, DSE, EFEMP2, ELN, FBLN5, FBN1, FKBP14, FLNA, LTBP4, PLOD1, PRDM5, PYCR1, RIN2, SLC39A13, SMAD2, SMAD3, TGFB2, TGFBR1, TGFBR2, TNXB, ZNF469

List of diseases covered by the panel
Lab method: NGS panel with CNV analysis
TAT: 6-9 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of Ehlers-Danlos syndrome types and other genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Ehlers-Danlos syndrome (EDS) is a group of rare disorders affecting connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. The 2017 classification describes 13 types of EDS. The symptoms depend upon the specific type of EDS. An unusually large range of joint movement occurs in most forms of EDS and many individuals with the EDS have soft, velvety skin that is highly stretchy (elastic) and fragile. The vascular type of disease causes bleeding problems, the cardiac-valvular type causes severe problems with the valves that control the movement of blood through the heart, and people with the kyphoscoliotic type experience severe curvature of the spine.

The test covers the known genetic causes of EDS types and a range of other genetically/phenotypically related disorders.

Depending on the type of EDS it could be inherited in an autosomal dominant or autosomal recessive pattern.

The combined prevalence of all types of EDS is estimated to affect 1 in 2500 to 5000 individuals in the general population. Most common are hypermobile and classical forms affecting 1 in 5,000 to 20,000 people and 1 in 20,000 to 40,000 people, respectively. Other forms of EDS are extremely rare.

References:

Byers PH. Vascular Ehlers-Danlos Syndrome. 1999 Sep 2 [Updated 2019 Feb 21]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1494/
Levy HP. Ehlers-Danlos Syndrome, Hypermobility Type. 2004 Oct 22 [updated 2016 Mar 31]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1279/
Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8-26. doi:10.1002/ajmg.c.31552. PMID: 28306229
Malfait F, Wenstrup R, De Paepe A. Ehlers-Danlos Syndrome, Classic Type. 2007 May 29 [updated 2011 Aug 18]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1244/
Pepin MG, Murray ML, Byers PH. Vascular Ehlers-Danlos Syndrome. 1999 Sep 2 [updated 2015 Nov 19]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1494/
Cannaerts E, Kempers M, Maugeri A, et al. Novel pathogenic SMAD2 variants in five families with arterial aneurysm and dissection: further delineation of the phenotype. J Med Genet. 2019;56(4):220-227. doi:10.1136/jmedgenet-2018-105304. PMID: 29967133

Familial Thoracic Aortic Aneurysm and Dissection and Related Syndromes NGS panel

Published 28/05/2015

Familial Thoracic Aortic Aneurysm and Dissection
and Related Syndromes
NGS panel

Genes
(full
coding region):		 ACTA2, BGN, COL3A1, COL5A1, FBN1, LOX, MAT2A, MFAP5, MYH11, MYLK, NOTCH1, PRKG1, SLC2A10, SMAD3, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3

List of diseases covered by the panel
Lab method: NGS panel with CNV analysis
TAT: 6-9 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Deletion/duplication analysis

Genes: FBN1, TGFBR2
Lab method: MLPA
TAT: 4-6 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

2 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Indications for genetic testing:

  1. Confirmation of clinical diagnosis
  2. Differential diagnosis of familial TAAD, Marfan syndrome, Loeys-Dietz syndrome and genetically/phenotypically related disorders
  3. Predictive testing for at-risk asymptomatic family members
  4. Prenatal diagnosis for known familial mutation
  5. Genetic counseling

Familial Thoracic Aortic Aneurysm and Dissection (TAAD) is characterized by enlargement of ascending aorta leading to an aortic dissection or, rarely, aortic rupture. Aortic dilatation is usually the first manifestation of the disease that may lead to the development of aortic aneurysm and aortic dissection. Aortic dissection occurs when the tear in the aorta wall allows blood to flow between the aorta’s inner and outer walls. Aortic dissections originate primarily in the ascending aorta (Stanford type A), but also can occur in the descending thoracic aorta (Stanford type B).

Thoracic aortic aneurysms may be asymptomatic. Aneurysms and dissections can occur as an isolated cardiovascular abnormality or are related to genetic disorders such as Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, and others.

Familial TAAD is inherited in an autosomal dominant pattern. Up to 19% of persons with TAAD have a first-degree relative with thoracic aortic disease.

References:

Albornoz G et al. Familial thoracic aortic aneurysms and dissections–incidence, modes of inheritance, and phenotypic patterns. Ann Thorac Surg. 2006;82:1400–5.
Milewicz DM and Regalado E. Thoracic Aortic Aneurysms and Aortic Dissections. GeneReviews® 2003 February 13 (Updated 2012 January 12).