摘要： 目的 总结国内结节性硬化症（TSC）临床表现、基因突变位点分布特点和突变类型，探讨基因型与临床表型之间的关系。方法 共检出3 例存在致病性基因突变的结节性硬化症患儿，同时收集国内160 例有明确致病性基因突变的结节性硬化症患者，对其基因检测结果和临床资料进行汇总分析。结果 共163 例患者中31 例（19.02%）发生TSC1 基因突变，第15、21、18 号外显子分别占32.26%（10/31）、16.13%（5/31）、12.90%（4/31），132 例（80.98%）发生TSC2 基因突变，第37、40、33 号外显子分别占9.85%（13/132）、7.58%（10/132）、6.82%（9/132）。TSC1 突变碱基置换率为41.94%（13/31）、TSC2 突变为52.27%（69/132）。男性患者室管膜下结节或钙化灶发生率（χ² = 8.016，P = 0.005）、散发性患者大脑皮质结节发生率（χ² = 6.273，P = 0.012）、TSC2 基因突变患者色素脱失斑发生率（χ² = 6.756，P = 0.009）和错义突变患者面部血管纤维瘤发生率（χ² = 4.438，P = 0.035），分别高于女性患者、家族性患者、TSC1 基因突变患者和其他突变类型患者。结论 TSC1 基因突变主要发生于第15、21、18 号外显子，TSC2 基因突变以第37、40、33 号外显子多见。其基因型与临床表型间关系的研究有助于结节性硬化症的个体化治疗和预后评价。

关键词: 结节性硬化症, 基因型, 突变, 表型

Abstract: Objective  To summarize the clinical features of tuberous sclerosis complex (TSC), the distribution and description of TSC gene, and to probe into the correlation of genotype with phenotype.  Methods  According to the 1998 International Tuberous Sclerosis Complex Diagnostic Criteria, a total of 163 TSC patients with pathogenic mutation in TSC gene (3 cases were detected in our hospital, and the other 160 cases were collected from other institutions in China) were enrolled, and their gene detection results and clinical data were analyzed.  Results  Among 163 cases, TSC1 mutation (31 cases) accounted for 19.02% [32.26% (10/31) in exon 15, 16.13% (5/31) in exon 21, 12.90% (4/31) in exon 18], and TSC2 mutation (132 cases) accounted for 80.98% [9.85% (13/132) in exon 37, 7.58% (10/132) in exon 40, 6.82%(9/132) in exon 33]. The proportion of base replacement in TSC1 was 41.94% (13/31), and 52.27% (69/132) in TSC2. Male patients exhibited significantly more subependymal nodules or calcifications than thefemale patients (χ² = 8.016, P = 0.005). Sporadic patients exhibited significantly more cortical tubers than familial patients (χ² = 6.273, P = 0.012). Patients with TSC2 mutations had significantly higher frequencies of hypomelanotic macules than patients with TSC1 mutations (χ² = 6.756, P = 0.009). Patients with missense mutations were more likely to have facial angiofibromas compared with patients with other mutations (χ² = 4.438, P = 0.035).  Conclusions  Exon 15, 21 and 18 of TSC1 and exon 37, 40 and 33 of TSC2 accounted for higher percentage of mutations. Correlating genotypes with phenotypes should facilitate the individualized treatment and prognostic assessment of tuberous sclerosis complex.

Key words: Tuberous sclerosis, Genotype, Mutation, Phenotype