A 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.

许多病例/家庭报告提出PTCH2是推定的 Gorlin 综合征 (GS) 基因，但缺乏支持这一点的证据。我们评估了我们的 21 个PTCH1/SUFU阴性 GS 家族的PTCH2变体队列，并评估了来自报告病例/家族和人口数据的当前证据。在我们的PTCH1/SUFU变异阴性 GS 队列中（占总数的 25%），未发现致病性或可能致病性PTCH2变异。此外，之前发布的PTCH2使用当前指南，GS 家族/病例中的变异可能被认为是致病性的或可能是致病性的。GS 家族中缺乏明确的致病变异，而普通人群中功能丧失 (LoF) 变异的高频率，包括没有临床表型的纯合 LoF 变异的存在，意味着PTCH2是 GS是站不住脚的基因。PTCH2不应包含在 GS 基因诊断组中。