复合杂合突变型脑腱黄瘤病1例及其基因型和临床表型关系探讨

Heterozygous-mutation induced cerebrotendinous xanthomatosis and correlation of genotype with clinical phenotype

目的 :分析1例复合杂合型突变所致脑腱黄瘤病(cerebrotendinous xanthomatosis, CTX)及初步探讨该病基因型与临床表型关系。方法:收集1例临床诊断为CTX患者的临床资料,并对患者及其父母进行基因测序。结果:患者具备CTX典型临床表现。基因检测显示exon2(NM_000784.3:c.379C>T; NP_000775.1:p. Arg127Trp)和exon7(NM_000784.3:c.1214G>A; NP_000775.1:p. Arg405Gln)处各存在1个突变。其母亲为exon2处突变携带者,父亲为exon7处突变携带者。头颅磁共振成像(magnetic resonance imaging, MRI)示双侧小脑半球齿状核-大脑脚-内囊后肢异常信号;踝关节MRI显示右跟腱后方富脂肪成分占位。高密度脂蛋白胆固醇(0.8 mmol/L)较参考范围(0.9～1.83 mmol/L)降低。结论:CTX基因型和临床表型之间存在一定关系。该例新发现复合杂合突变较单一突变可能导致不同的血胆固醇代谢过程。

Objective To analyze a case of heterozygous mutation induced cerebrotendinous xanthomatosis （CTX） and investigate the correlation between genotype and clinical phenotype. Methods The clinical data of a patient diagnosed as CTX and the gene sequencing of the patient and his parents were collected, and the correlation between genotype and clinical phenotype was analyzed. Results A patient with typical clinical manifestations of CTX was presented. Genetic testing demonstrated that the patient had heterozygous mutations located in exon2 （NM_000784.3： c.379C〉T; NP_000775.1： p. Arg127Trp） and exon7 （NM_000784.3： c.1214G〉A; NP 000775.1： p. Arg405Gln）, and his mother and father had exon2 mutation and exon7 mutation, respectively. Skull magnetic resonance imaging （MRI） revealed abnormal signals in bilateral dental nucleus-cerebral peduncles-posterior limb of the internal capsule. MRI of ankle joint established the existence of fat- rich tumor behind the right Achilles tendon. High density lipoprotein cholesterol （0.8 mmol/L） was lower than reference range （0.9-1.83 retool/L）. Conclusions Genotype of CTX had correlation with clinical phenotype. This newly found heterozygous mutation was probably different from single mutation in cholesterol metabolism process.