Diagnostic Test Directory

Molecular Genetics Laboratory

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Craniofrontonasal Syndrome, CFNS (EFNB1 Deletion/Duplication and Sequence Analysis)

  • LIS Mnemonic: MBEFNB1FS

    Collect

    Whole blood in a purple top (EDTA) tube is preferred. Extracted DNA is acceptable

    Volume Required

    5 ml whole blood; 2 ug extracted DNA

    Minimum Required

    3 ml whole blood

    Transport

    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.

    Stability

    Whole blood can be refrigerated until shipment.

    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.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm

Reported

4-6 weeks

CPT

81479 x 2

Disease Information

Clinical Features:

Craniofrontonasal syndrome (CFNS) is an X-linked dominant disorder whose main clinical manifestations include coronal synostosis, hypertelorism, clefting of the nasal tip and various skeletal anomalies. Expression of CFNS is more severe in heterozygous females than in hemizygous males. Heterozygous females can display multiple cranial and extra-cranial features including, but not limited to: craniofacial asymmetry, craniosynostosis, bifid nasal tip, hypertelorism, and abnormalities of the thoracic skeleton and digits. Hemizygous males have no or only mild manifestations such as hypertelorism.

Molecular Genetics:

Loss-of-function mutations in EFNB1 located in Xq13.1 cause CFNS. Published mutations include frameshift, nonsense, missense, splice-site mutations, and partial/whole gene deletions. Mutations have been identified in all 5 exons, however more than half of mutations are located in exon 2. Somatic mosaicism has been described in 10-15% of families; thus, it may not always be possible to detect the pathogenic EFNB1 mutation in the first affected family member.

Test Methods:

We offer DNA sequence analysis and deletion/duplication testing of the entire coding region. These tests can be ordered as a panel or individually. PCR amplification and sequence analysis is performed on all coding exons including splice junctions. The patient’s gene sequence is then compared to a reference sequence. Sequence variants are classified as mutations, variants of unknown significance or benign variants unrelated to disease. Variants of unknown significance may warrant further studies in the patient and other family members. Mutations in promoters, deep intronic regions and other regulatory regions will not be identified with this assay. Large deletions in the EFNB1 gene will be detected using a multiplex ligation-dependent probe amplification assay (MLPA).

Detection Rate:

Mutations in the EFNB1 gene are identified in ~86-89% of individuals with a clinical diagnosis of CFNS. The analytical sensitivity of sequencing and MLPA is ~99%.

Related Tests:

Known mutation analysis of the EFNB1 gene is available to family members for mutations previously identified by sequence analysis or deletion/duplication analysis.

Results:

Test results with interpretation will be mailed and/or faxed to the referring physician following completion of the test. Additional reports will be provided as requested.

Utility:

The clinical utility of the assay is to support a clinical diagnosis of the disease, facilitate genetic counseling, assess the risk to other first degree relatives and to facilitate testing of at - risk family members.

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215-590-5221