ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000016.9) (NC_000016.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
10835629 Bignell et al (2000) identified CYLD as the causal gene for familial cylindromatosis (FC), an inherited condition that manifests as benign cutaneous adnexal tumors. Sequence analysis of 21 affected families identified 9 frameshifting mutations, 9 nonsense mutations, and 3 splice site alterations. All variations segregated with the condition, are predicted to result in loss of function variation, and are not observed or observed very infrequently in population databases.
15854031 Bowen et al (2005) documents three families with familial benign skin tumors with clinical diagnoses of Brooke-Speigler Syndrome (BSS), FC, and two families with multiple familial trichoepitheliomas (MFT). Five families were found to have rare nonsense or frameshift variants in CYLD. No CYLD variant was identified in the sixth family.
20132422 Kazakov (2010) reports a patient with germline putative splicing variant (c.1684+1G>A) in CYLD and multiple benign lesions. In addition to the benign lesions, the patient had two basal cell carcinomas that demonstrated loss of heterozygosity for the CYLD locus. This case, and others, demonstrates the potential for the benign skin lesions associated with CYLD-associated cutaneous syndromes to transform into malignancies.

Haploinsufficiency phenotype comments:

Transformation of the benign tumors present in CYLD-associated cutaneous syndromes has been reported, starting with Gerretsen et al 1993 (PMID 7688655). Estimated rates of malignant transformation range from 5-10% (Kazakov 2016, PMID 26971504).

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No evidence for triplosensitivity