Supplementary Material for: A novel PTCH1 non-canonical splice region variant associated with Gorlin syndrome: case report

Introduction: Gorlin syndrome (GS) is a rare autosomal dominant condition that predisposes to cutaneous basal cell carcinomas, jaw keratocysts, and skeletal anomalies. Most patients with GS have a heterozygous pathogenic variant in the PTCH1 gene although a minor subset have a pathogenic variant in the SUFU gene.
Case Presentation: We report a 34-year-old woman meeting clinical diagnostic criteria for GS and with an affected father who also meets diagnostic criteria. Both had a novel germline splice-region variant that was originally classified as a variant of uncertain significance.
Conclusion: We used cDNA analysis to provide additional evidence to allow re-classification of the non-canonical splice variant and provide a formal genetic diagnosis that can also be used for family planning and to screen at-risk relatives.

引言：戈林综合征（Gorlin syndrome, GS）是一种罕见的常染色体显性遗传病，患者易罹患皮肤基底细胞癌、颌骨角化囊肿及骨骼发育异常。绝大多数GS患者存在PTCH1基因的杂合致病性变异，仅少数患者的致病变异位于SUFU基因中。
病例报告：本研究报告1例符合GS临床诊断标准的34岁女性患者，其父亲同样符合该病诊断标准且已患病。二人均携带1种新型生殖系剪接区变异，该变异最初被归类为意义未明变异（variant of uncertain significance）。
结论：本研究通过互补脱氧核糖核酸（complementary DNA, cDNA）分析获取了额外证据，使得该非经典剪接变异得以重新分类，并确立了正式的遗传学诊断。该诊断结果可用于家族生育规划以及对高危亲属进行筛查。