Marfan Syndrome Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: CA0801

The Blueprint Genetics Marfan Syndrome Panel is a 25-gene test for genetic diagnostics of patients with clinical suspicion of Marfan syndrome or other disorder that resembles Marfan syndrome. This Panel covers diseases such as arterial tortuosity syndrome, congenital contractural arachnodactyly, Ehlers-Danlos syndrome, Loeys-Dietz syndrome, Marfan syndrome and Shprintzen-Goldberg syndrome.

Disorders that share phenotypic features with Marfan syndrome are inherited in an autosomal dominant and autosomal recessive manner. Genetic diagnosis has substantial significance for the patient and his family as it forms the basis for genetic counseling and can be used to determine risk of vascular complications and assessment of treatment strategies.

About Marfan Syndrome

The diagnosis of Marfan syndrome can be difficult as many of the features are also identified in normal population, features appear in an age-dependent manner and there is substantial phenotypic variability between the patients. There is also considerable overlap with other connective-tissue disorders such as congenital contractural arachnodactyly (CCA), Loeys-Dietz syndrome (LDS), Ehlers-Danlos syndrome, arterial tortuosity syndrome and Shprintzen-Goldberg syndrome. The Marfan Panel is designed as a genetic diagnostic tool for patients suffering from clinical features of Marfan syndrome. The two major features of Marfan syndrome are vision problems caused by a dislocated lens (ectopia lentis) in one or both eyes and aortic aneurysms and dissection. Aortic aneurysm and dissection can be life threatening. Mitral valve regurgitation is another cardiovascular defect associated with disorder. Individuals with Marfan syndrome are usually tall and slender, have elongated fingers and toes, and have an arm span that exceeds their body height. Other common features include crowded teeth, a long and narrow face, dural ectasia, an abnormal curvature of the spine, and chest abnormalities. The features of Marfan syndrome can become apparent anytime between infancy and adulthood. Depending on the onset and severity of signs and symptoms, Marfan syndrome can be fatal early in life; however, the majority of affected individuals survive into mid- to late adulthood.

Availability

Results in 3-4 weeks.

Genes in the Marfan Syndrome Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ADAMTSL4Ectopia lentis, isolatedAR720
CBSHomocystinuria due to cystathionine beta-synthase deficiencyAR51192
COL1A1Ehlers-Danlos syndrome, Osteogenesis imperfectaAD120883
COL1A2Ehlers-Danlos syndrome, cardiac valvular form, Osteogenesis imperfectaAD79473
COL2A1Avascular necrosis of femoral head, Stickler syndrome, Rhegmatogenous retinal detachment, Epiphyseal dysplasia, with myopia and deafness, Czech dysplasiaAD106537
COL3A1Ehlers-Danlos syndromeAD452617
COL5A1Ehlers-Danlos syndromeAD43133
COL5A2Ehlers-Danlos syndromeAD1223
COL9A1Stickler syndromeAR34
COL9A2Stickler syndromeAR512
COL11A1Marshall syndrome, Fibrochondrogenesis, Stickler syndromeAD/AR1876
COL18A1Knobloch syndromeAR1329
FBN1MASS syndrome, Shprintzen-Goldberg syndrome, Marfan syndromeAD5192056
FBN2Congenital contractural arachnodactyly (Beals syndrome)AD3085
MED12Ohdo syndrome, Mental retardation, with Marfanoid habitus, FG syndrome, Opitz-Kaveggia syndrome, Lujan-Fryns syndromeXL1719
PLOD1Ehlers-Danlos syndromeAR1637
SKIShprintzen-Goldberg syndromeAD1520
SLC2A10Arterial tortuosity syndromeAR2130
SMAD3Aneurysms-osteoarthritis syndrome, Loeys-Dietz syndromeAD2650
TGFB2Loeys-Dietz syndromeAD1524
TGFB3Loeys-Dietz syndrome (Reinhoff syndrome), Arrhythmogenic right ventricular dysplasiaAD818
TGFBR1Loeys-Dietz syndromeAD2567
TGFBR2Loeys-Dietz syndromeAD54130
UPF3BMental retardation, syndromicXL516
VCANWagner diseaseAD1119

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Blueprint Genetics offers a comprehensive Marfan syndrome panel that covers classical genes associated with aortic anaurysm, ruptured, abdominal aorta, aortic aneurysm, ruptured, thracic aorta, aortic aneurysm, ruptured, unspecific site, aortic aneurysm, thoracic aorta, aortic disection, thorcic aorta, arterial tortuosity syndrome, congenital contractural arachnodactyly, Ehlers-Danlos syndrome, Loeys-Dietz syndrome, Marfan syndrome and Shprintzen-Goldberg syndrome. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ81410
DEL/DUP81411


ICD codes

Commonly used ICD-10 codes when ordering the Marfan Syndrome Panel

ICD-10Disease
Q87.40Marfan syndrome
Q87.89Loeys-Dietz syndrome
Q87.89Shprintzen-Goldberg syndrome
Q79.6Ehlers-Danlos syndrome
Q87.89Arterial tortuosity syndrome
Q87.89Congenital contractural arachnodactyly

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.