Abstract：
OBJECTIVE: To analyse the aetiology and pathogenesis of Gorlin-Goltz syndrome (GS; also known as nevoid basal cell carcinoma syndrome [NBCCS] or basal cell nevus syndrome [BCNS]) in a Chinese family.
METHODS: Whole-exome sequencing (WES) was performed on genomic DNA samples from the subjects in a family, followed by the investigation of pathogenesis via bioinformatic approaches and conformational analysis.
RESULTS: A novel heterozygous non-frameshift deletion patched 1 (PTCH1) [NM_000264: c.3512_3526del (p.1171_1176del)] was identified by WES and further validated by Sanger sequencing. Bioinformatic and conformational analysis showed that the mutation caused altered PTCH1 protein structure, which may be related to functional abnormalities.
CONCLUSIONS: This study expands the mutation spectrum of PTCH1 in GS and facilitates the early diagnosis and screening of GS. PTCH1 [c.3512_3526del (p.1171_1176del)] may cause structural abnormalities and functional disabilities, leading to GS in families.
METHODS: Whole-exome sequencing (WES) was performed on genomic DNA samples from the subjects in a family, followed by the investigation of pathogenesis via bioinformatic approaches and conformational analysis.
RESULTS: A novel heterozygous non-frameshift deletion patched 1 (PTCH1) [NM_000264: c.3512_3526del (p.1171_1176del)] was identified by WES and further validated by Sanger sequencing. Bioinformatic and conformational analysis showed that the mutation caused altered PTCH1 protein structure, which may be related to functional abnormalities.
CONCLUSIONS: This study expands the mutation spectrum of PTCH1 in GS and facilitates the early diagnosis and screening of GS. PTCH1 [c.3512_3526del (p.1171_1176del)] may cause structural abnormalities and functional disabilities, leading to GS in families.
摘要：
目的：分析一个中国家族的Gorlin-Goltz综合征（GS；又称中性基底细胞癌综合征[NBCCS]或基底细胞痣综合征[BCNS]）的病因和发病机制。
方法：对一个家族受试者的基因组DNA样本进行全外显子组测序（WES），随后通过生物信息学方法和构象分析研究发病机制。
结果：通过WES鉴定了一种新的杂合非移码缺失1（PTCH1）[NM_000264：c.3512_3526del（p.1171_1176del）]，并通过Sanger测序进一步验证。生物信息学和构象分析表明该突变导致PTCH1蛋白结构改变,这可能与功能异常有关。
结论：本研究扩展了PTCH1在GS中的突变谱，有利于GS的早期诊断和筛查。PTCH1[c.3512_3526del（p.1171_1176del）]可能会导致结构异常和功能障碍，导致家庭中的GS。
方法：对一个家族受试者的基因组DNA样本进行全外显子组测序（WES），随后通过生物信息学方法和构象分析研究发病机制。
结果：通过WES鉴定了一种新的杂合非移码缺失1（PTCH1）[NM_000264：c.3512_3526del（p.1171_1176del）]，并通过Sanger测序进一步验证。生物信息学和构象分析表明该突变导致PTCH1蛋白结构改变,这可能与功能异常有关。
结论：本研究扩展了PTCH1在GS中的突变谱，有利于GS的早期诊断和筛查。PTCH1[c.3512_3526del（p.1171_1176del）]可能会导致结构异常和功能障碍，导致家庭中的GS。
