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

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

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 2 1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 6 9%。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 6 71<A >和 6 72 <T >)发生缺失移码突变 6 71delAT ,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 6

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.