Abstract
AbstractA number of case/family reports have proposed PTCH2 as a putative Gorlin Syndrome (GS) gene, but evidence to support this is lacking. We assessed our cohort of 21 PTCH1/SUFU negative GS families for PTCH2 variants and assessed current evidence from reported cases/families and population data. In our PTCH1/SUFU variant negative GS cohort (25% of total), no pathogenic or likely pathogenic PTCH2 variants were identified. In addition, none of the previously published PTCH2 variants in GS families/cases could be considered pathogenic or likely pathogenic using current guidelines. The absence of clear pathogenic variants in GS families and the high frequency of Loss-of-function (LoF) variants in the general population, including the presence of homozygous LoF variants without a clinical phenotype, mean that it is untenable that PTCH2 is a GS gene. PTCH2 should not be included in panels for genetic diagnosis of GS.
Funder
Manchester Biomedical Research Centre
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics(clinical),Oncology,Genetics
Reference12 articles.
1. Evans DG, Farndon PA (1993) Nevoid basal cell carcinoma syndrome. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong CT et al (eds) GeneReviews(R). University of Washington, Seattle
2. Smith MJ, Beetz C, Williams SG, Bhaskar SS, O’Sullivan J, Anderson B, Daly SB, Urquhart JE, Bholah Z, Oudit D, Cheesman E, Kelsey A, McCabe MG, Newman WG, Evans DG (2014) Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations. J Clin Oncol 32:4155–4161
3. Evans DG, Oudit D, Smith MJ, Rutkowski D, Allan E, Newman WG, Lear JT (2017) First evidence of genotype-phenotype correlations in gorlin syndrome. J Med Genet 54:530–536
4. Smyth I, Narang MA, Evans T, Heimann C, Nakamura Y, Chenevix-Trench G, Pietsch T, Wicking C, Wainwright BJ (1999) Isolation and characterization of human patched 2 (PTCH2), a putative tumour suppressor gene inbasal cell carcinoma and medulloblastoma on chromosome 1p32. Hum Mol Genet 8:291–297
5. Fan Z, Li J, Du J, Zhang H, Shen Y, Wang CY, Wang S (2008) A missense mutation in PTCH2 underlies dominantly inherited NBCCS in a Chinese family. J Med Genet 45:303–308
Cited by
8 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献