Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Clinical Features
Marfan syndrome [OMIM# 154700] is an autosomal dominant connective tissue disorder caused by pathogenic variants in the FBN1 gene. It is characterized by a variable presentation of pectus deformations, tall stature, joint laxity/contractures, myopia, lens dislocation, and aortic dilatation or dissection. There is a broad phenotypic spectrum and variable expressivity even among affected individuals of the same family.
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
Next generation sequencing (NGS) of FBN1 detects a disease-causing variant in 70-93% of individuals meeting clinical diagnostic criteria for Marfan syndrome [GeneReviews 2022, PMID: 20301510; Loeys 2010, PMID: 20591885]. Partial to whole gene copy number variants account for approximately 2-9% of molecular diagnoses of Marfan syndrome [GeneReviews 2022, PMID: 20301510]. The detection rate for allelic disorders, including acromicric dysplasia, geleophysic dysplasia 2, Marfan lipodystrophy syndrome, MASS syndrome, stiff skin syndrome, and Weill-Marchesani syndrome 2, is unknown.
Utility
The clinical utility of the assay is to support a clinical diagnosis of the disease, to facilitate genetic counseling, to assess the risk to other first degree relatives, and to facilitate testing of at-risk family members. Molecular confirmation of a diagnosis may help guide recommendations for medical management and screening, and may help avoid unnecessary procedures.
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis is based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
Marfan syndrome is an autosomal dominant disorder caused by pathogenic mutations in the fibrillin 1 gene (FBN1). FBN1 pathogenic variants are associated with a broad phenotypic spectrum with mildly affected individuals having isolated features of Marfan syndrome and severely affected individuals having a severe presentation with rapid progression in multiple organ systems [GeneReviews 2022; PMID: 20301510]. Approximately 75% of individuals with Marfan syndrome have an affected parent. The remaining ~25% of cases of Marfan syndrome result from a de novo pathogenic FBN1 variant. Marfan syndrome is associated with extensive intrafamilial clinical variability. Variants in FBN1 are also associated with several other autosomal dominant disorders including acromicric dysplasia, geleophysic dysplasia 2, Marfan lipodystrophy syndrome, MASS syndrome, stiff skin syndrome, and Weill-Marchesani syndrome 2. This panel includes sequence and copy number analyses of the FBN1 gene.
CPT Codes
81408
Collection
Collect
Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Ordering
Clinical Features
Marfan syndrome [OMIM# 154700] is an autosomal dominant connective tissue disorder caused by pathogenic variants in the FBN1 gene. It is characterized by a variable presentation of pectus deformations, tall stature, joint laxity/contractures, myopia, lens dislocation, and aortic dilatation or dissection. There is a broad phenotypic spectrum and variable expressivity even among affected individuals of the same family.
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
Next generation sequencing (NGS) of FBN1 detects a disease-causing variant in 70-93% of individuals meeting clinical diagnostic criteria for Marfan syndrome [GeneReviews 2022, PMID: 20301510; Loeys 2010, PMID: 20591885]. Partial to whole gene copy number variants account for approximately 2-9% of molecular diagnoses of Marfan syndrome [GeneReviews 2022, PMID: 20301510]. The detection rate for allelic disorders, including acromicric dysplasia, geleophysic dysplasia 2, Marfan lipodystrophy syndrome, MASS syndrome, stiff skin syndrome, and Weill-Marchesani syndrome 2, is unknown.
Utility
The clinical utility of the assay is to support a clinical diagnosis of the disease, to facilitate genetic counseling, to assess the risk to other first degree relatives, and to facilitate testing of at-risk family members. Molecular confirmation of a diagnosis may help guide recommendations for medical management and screening, and may help avoid unnecessary procedures.
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis is based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
Marfan syndrome is an autosomal dominant disorder caused by pathogenic mutations in the fibrillin 1 gene (FBN1). FBN1 pathogenic variants are associated with a broad phenotypic spectrum with mildly affected individuals having isolated features of Marfan syndrome and severely affected individuals having a severe presentation with rapid progression in multiple organ systems [GeneReviews 2022; PMID: 20301510]. Approximately 75% of individuals with Marfan syndrome have an affected parent. The remaining ~25% of cases of Marfan syndrome result from a de novo pathogenic FBN1 variant. Marfan syndrome is associated with extensive intrafamilial clinical variability. Variants in FBN1 are also associated with several other autosomal dominant disorders including acromicric dysplasia, geleophysic dysplasia 2, Marfan lipodystrophy syndrome, MASS syndrome, stiff skin syndrome, and Weill-Marchesani syndrome 2. This panel includes sequence and copy number analyses of the FBN1 gene.
