CONNECTIVE TISSUE LABORATORY
MARFAN SYNDROME & RELATED
AORTIC ANEURYSM SYNDROMES
Center for Medical Genetics – Medical Research Building (MRB)
Ghent University Hospital
De Pintelaan 185
B-9000 Ghent
Belgium
Contact for clinical information:
 Dr. Julie De Backer and Prof. Anne De Paepe
Julie.DeBacker@UGent.be and Anne.DePaepe@UGent.be
Contact the laboratory: E-mail: connective_tissue@medgen.ugent.be
 Lic. Sofie Symoens - Prof. Paul Coucke - Dr. Julie De Backer Prof. Dr. Anne De Paepe
Sofie.Symoens@UGent.be /Paul.Coucke@UGent.be
Receipt of samples: Tel: 0032-(0)9-332 24 77 – Fax: 0032-(0)9-332 65 49
Website: http://medgen.ugent.be
1
CMG-H9.1-B4
Version: 1
Date: 3 October 2011
CONNECTIVE TISSUE LABORATORY
Center for Medical Genetics –Ghent University Hospital – MRB – De Pintelaan 185 – B-9000 Ghent, Belgium
Department Chair: Prof. Dr. A. De Paepe – Supervisor connective tissue lab: Prof. Dr. P. Coucke
MARFAN SYNDROME & RELATED AORTIC ANEURYSM SYNDROMES
A. TESTING FOR KNOWN MUTATONS
TAT
Mutation testing in family members
6 weeks
Prenatal diagnosis, including the test for maternal contamination
10 days
B. MUTATION SCANNING
Disorder
Test
TAT
Marfan syndrome and related disorders
FBN1 gDNA mutation screening**
FBN1 MLPA**
3 months
4 month
Loeys-Dietz syndrome (LDS)
TGFBR1 and TGFBR2 gDNA mutation screening***
TGFBR1/2 MLPA***
3 months
4 months
Beals-Hecht syndrome (CCA)
FBN2 gDNA mutation screening (relevant exons)
4 months
Familial Thoracic Aortic Aneurysm (FTAA), ACTA2 gDNA mutation screening
FTAA with Osteoarthritis (AOS),
SMAD3 gDNA mutation screening
FTAA with patent ductus arteriosus
MYH11 gDNA mutation screening
4 months
4 months
4 months
Arterial Tortuosity Syndrome
4 months
SLC2A10 gDNA mutation screening
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CMG-H9.1-B4
Version: 1
Date: 3 October 2011
CONNECTIVE TISSUE LABORATORY
Center for Medical Genetics –Ghent University Hospital – MRB – De Pintelaan 185 – B-9000 Ghent, Belgium
Department Chair: Prof. Dr. A. De Paepe – Supervisor connective tissue lab: Prof. Dr. P. Coucke
GUIDELINES AND PRACTICAL INFORMATION
The Marfan syndrome is a heritable autosomal dominant connective tissue disorder caused by
mutations in FBN1, the gene encoding fibrillin-1, one of the principal components of the
microfibrils that compose the elastic fibers. The Marfan syndrome is a pleiotropic genetic
disorder with manifestations in the skin, the skeleton, the cardiovascular system and the lungs.
Usually, the diagnosis can be established on clinical basis according to the revised Ghent criteria
for Marfan syndrome. In patients for whom the diagnostic criteria for Marfan syndrome are
fulfilled molecular analysis of FBN1 reveals the disease-causing mutation in approximately 92%
of patients. It remains unclear whether the lack of full sensitivity of this test relates to an
atypical location of FBN1 mutations in some individuals or to locus heterogeneity. MLPA
analysis of the FBN1 gene reveals at least in 3% of the patients a deletion or insertion.
Although it is still unclear for Loeys-Dietz syndrome (LDS) in which percentage mutations in the
genes TGFBR1 or TGRBR2 are identified, there is no doubt that in the majority of patients that
are clinically diagnosed with LDS, mutations in one of the two genes are identified.
Familial TAAD (FTAAD) is diagnosed based on the presence of dilatation and/or dissection of the
thoracic aorta, absence of clinical features of Marfan syndrome, Loeys-Dietz syndrome, or
vascular Ehlers-Danlos syndrome, and presence of a positive family history of TAAD. However,
locus heterogeneity is evident and to date only about 20% of FTAAD is accounted for by
mutations in known genes as FBN1, TGFBR2, TGFBR1, MYH11, ACTA2, SMAD3. Molecular
genetic testing for all these genes is offered in our lab.
REASONS FOR REFERRAL

Confirmation of a clinically suspected diagnosis (mutation scanning).

Genetic counselling for at-risk relatives. For this purpose, the familial mutation should
have been identified previously.

Prenatal diagnosis (preferentially offered after genetic counselling). The mutation in the
affected parent should have been identified.
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CMG-H9.1-B4
Version: 1
Date: 3 October 2011
CONNECTIVE TISSUE LABORATORY
Center for Medical Genetics –Ghent University Hospital – MRB – De Pintelaan 185 – B-9000 Ghent, Belgium
Department Chair: Prof. Dr. A. De Paepe – Supervisor connective tissue lab: Prof. Dr. P. Coucke
SAMPLING INSTRUCTIONS AND TECHNICAL INFORMATION

DNA or EDTA blood: Minimum 20µg DNA or 5ml EDTA-blood should be sent to our
laboratory by express mail (FedEx / UPS). Prenatal samples (fetal DNA, chorion villi,or
amniocytes) must be sent with a sample (DNA or EDTA blood) of the mother. It is very
important to wrap the sample safely! Receipt of the samples will be confirmed by email. For prenatal diagnosis: please contact the laboratory prior to sending the samples !

Mutation scanning of the exons of the different genes is performed by fluorescent
bidirectional sequencing or in combination with High Resolution Melting Analysis
(HRM). In case mutation screening is negative and the clinical information is convincing
for the phenotype, MLPA analysis (only for FBN1 and TGFBR1/TGFBR2) can be
performed in order to detect genomic deletions and/or insertions. Also testing for other
genes can be considered if appropriate. Before starting a new analysis a new request
form is necessary.
For FBN2 standard only exon 15, exons 22-33 and exons 35-36 are analysed. On request,
the sequencing of the complete FBN2 gene can be done.
ADDITIONAL DOCUMENTS
 Clinical checklist (CMG-H9.3-B9)

Informed consent form (CMG-H9.3-B11 or CMG-H9.3-B12 = toestemmingsformulier
bindweefselaandoeningen)
Prior to the biochemical and molecular analysis, you will be asked to fill a clinical checklist. This
will enable us to decide which molecular test is the most appropriate to start with.
We also require the informed consent of the patient, which is mandatory before the analysis is
started.
TURN-AROUND-TIME AND COST

Prices on request.
4
CMG-H9.1-B4
Version: 1
Date: 3 October 2011
CONNECTIVE TISSUE LABORATORY
Center for Medical Genetics –Ghent University Hospital – MRB – De Pintelaan 185 – B-9000 Ghent, Belgium
Department Chair: Prof. Dr. A. De Paepe – Supervisor connective tissue lab: Prof. Dr. P. Coucke

Turn-around times start from the receipt of all required samples. Some tests are
performed sequentially, in which case the TAT should be added up.

The VAT-number of your institution is mandatory!

Confirmation of a mutation in a second independent sample of the proband is not
charged.
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CMG-H9.1-B4
Version: 1
Date: 3 October 2011