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Molecular Genetics Laboratory

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Familial Cylindromatosis Tier 1 (CYLD exons 16-20)

  • Synonyms: Brooke-Spiegler syndrome (BSS), and multiple familial trichoepithelioma (MFT1)
  • LIS Mnemonic: MBCYLDTIER1


    Collect whole blood in a purple top (EDTA) tube.

    Volume Required


    Minimum Required



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


    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


4-6 weeks



Disease Information

Clinical Features:

The autosomal dominant disorders classically referred to as familial cylindromatosis, Brooke-Spiegler syndrome (BSS), and multiple familial trichoepithelioma (MFT1) were originally described as distinct clinical entities. Patients with BSS develop multiple skin appendage tumors including cylindromas, trichoepitheliomas, and spiradenomas. Patients with familial cylindromatosis have only cylindromas, and those with MFT1 have only trichoepitheliomas. However, because these disorders show overlapping phenotypic features, and because different manifestations of each have been described within a single family, many consider these disorders to represent a phenotypic spectrum of a single disease entity (Young et al. 2006).

Molecular Genetics:

Germline mutations in the tumor suppressor CYLD gene have been identified in all three disorders. The majority of the mutations result in truncated proteins, and most mutations were located between exons 9 to 20, encoding the NEMO binding site and the catalytic domain.

Test Methods:

We offer DNA sequence analysis of exons 16 -20 of the CYLD gene. PCR amplification and sequence analysis is performed on the select 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 the remaining coding exons of the CYLD gene, promoters, deep intronic regions and other regulatory regions will not be identified with this assay.

Detection Rate:

In 25 patients with skin appendage tumors, the mutation frequencies among distinct phenotypes was found to be 85% for BSS, 100% for FC, and 44% for MFT1 (Saggar et al. 2008; Blake et al. 2009). If a mutation is not identified in the Tier 1 test(exons 16-20, sequencing of the remaining coding exons is recommended. REFERENCES Blake et al. Update of cylindromatosis gene (CYLD) mutations in Brooke-Spiegler syndrome: novel insights into the role of deubiquitination in cell signaling. Hum. Mutat. 30: 1025-1036, 2009. Saggar et al. CYLD mutations in familial skin appendage tumours. J. Med. Genet. 45: 298-302, 2008. Young et al. CYLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes. Clin. Genet. 70: 246-249, 2006.

Related Tests:

CYLD Tier 2 (exons 9-15) CYLd Tier 3 (exons 4-8)


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


The clinical utility of such testing 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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