汉族家族性中枢神经系统海绵状血管瘤CCM1基因671delAT遗传突变的研究

目的探讨汉族家族性中枢神经系统海绵状血管瘤(FCCM)的遗传学特征和相关基因新突变.方法对临床收治的1例FCCM家族成员进行磁共振(MRI)影像学和神经系统检查,同时利用DNA直接测序法检测外周血标本中的CCM1基因突变.结果该家族成员共21人,已死亡3例,在存活者中有16人(89%)参加了调查.MRI检查发现患者共11例,外显率为69%.其中多发病灶7例、单发病灶4例,发病最小年龄为4岁,有不同程度的临床表现,未患病者5人.先证者及其他患病者CCM1基因第13号外显子的核苷酸序列第38<A>和39<T>位点(即在起始密码子以后的第671<A>和672<T>)发生缺失移码突变-671del AT,导致该基因编码KRIT1蛋白时出现错误,而在家系内未患病者和对照组中均未检测到上述突变.结论671del AT为一新发现的可以遗传的CCM1基因突变.

Identification of a novel inheritable CCM1 gene mutation of 671del AT in a Chinese family with cerebral cavernous malformation

OBJECTIVE: To investigate the hereditary characters of familial cerebral cavernous malformation (FCCM) and the novel gene mutation in a Chinese family. METHODS: Head MRI examination and clinical neurological check were performed on a Chinese family with one proband of FCCM, female, 27 years old, and 16 family members, 9 males and 12 females, and 19 controls, including patients with sporadic CCM and other diseases and healthy persons. DNA was extracted from the white blood cells of the peripheral blood of the subjects. PCR and DNA direct sequencing were used to detect the mutation in CCM1 gene. RESULTS: Head MRI found 11 FCCM patients in the 16 family members of the proband (69%), the youngest one being 4 years old, including multiple intracranial lesions in 7 patients and single lesion in 4. Relevant clinical manifestations were found in 6 out of the 11 family members. Nucleotide sequence analysis of the proband and other affected family members revealed a deletion frameshift mutation of A and T at nucleotides (nt) 671 and 672 in exon 13 of the CCM1 gene, resulting in truncated encoding KRIT1 protein. No mutation was detected in the healthy family members and the controls. CONCLUSION: A novel inheritable CCM1 gene mutation of 671del AT has been found in patients with FCCM.