摘要
目的分析并确定一个Canavan病家系天冬氨酸酰基转移酶(ASPA)基因突变及遗传特征。方法收集先证者及其家系成员临床资料,应用PCR方法对ASPA基因的所有6个外显子及其与内含子连接区域进行扩增,采用DNA直接测序与DNA限制性内切酶方法进行ASPA基因突变检测,确定基因突变的位点,分析基因型与表型的关系。结果该家系先证者的ASPA基因同时存在第1外显子c.187A>G(p.R63G)及第4外显子c.542C>A(p.P181H)的杂合改变,表型正常的先证者之妹发现携带第4外显子c.542C>A(p.P181H)的杂合改变,先证者之母ASPA基因带有第1外显子c.187A>G(p.R63G)的杂合改变,先证者之父第4外显子发现c.542C>A(p.P181H)的杂合改变。结论此家系中先证者为ASPA基因复合杂合突变致病,其c.187A>G(p.R63G)突变来自母亲,c.542C>A(p.P181H)突变来自父亲,其父母及胞妹均为表型正常的杂合子携带者。发现2个国际上尚未见报道的新ASPA基因突变(p.R63G与p.P181H),首次在国内明确了1例Canavan病的基因诊断。
Objective To analyze aspartoacylase （ASPA） gene mutations in one Chinese family with Canavan disease. Methods One patient was clinically diagnosed as Canavan disease in the investigated family. All 6 exons and exon - intron boundaries of ASPA gene were amplified in the family by polymerase chain reaction （PCR） and followed by direct DNA sequencing. The mutations had been proved by DNA restriction enzyme digestion of PCR - amplified fragments. Results Two heterozygous mutations of ASPA were identified c. 187A 〉 G （p. R63G） in exon 1 and c. 542C 〉 A（p. P181H） in exon 4 from proband. The heterozygous change c. 542C 〉 A（p. P181H） in exon 4 was found in the prohand＇s young sister with normal phenotype. The proband＇s mother had the heterozygous change c. 187A 〉 G（ p. R63G） and his father found the heterozygous variation e. 542C 〉 A（ p. P181H）. Conclusions The proband is heterozygous compound Canavan disease patient carrying on one allele with the c. 187A 〉 G（ p. R63G） mutation inherited from his mother, and the other＇allele with the c. 542C 〉 A （p. P181 H） from his father. The parents and his young sister are heterozygous carrier with normal phenotype. The p. R63 G and p. P181 H mutations are novel mutations not reported around world vet. This is the first renort about ASPA mutations in Canavan disease patient in China.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2009年第8期572-574,共3页
Journal of Applied Clinical Pediatrics
基金
国家“十一·五”重点项目资助(2006BAI05A07)
北京市自然科学基金项目资助(08G1469)
国家科技部“973”项目资助(2007CB5119004)
国际合作遗传研究培训基金项目资助(NIH/FIC,D43TW06176)
