中国人恶性高热家系蓝尼定受体-1基因的筛查

Screening of the ryanodine receptor type 1 gene in a Chinese pedigree with malignant hyperthermia

目的筛查中国人恶性高热（MH）家系的蓝尼定受体-1（RYR1）基因。方法提取确诊为MH的先证者及家系其他成员外周血白细胞的基因组DNA，采用PCR扩增先证者RYR1基因的部分外显子，并进行直接测序，采用FokⅠ限制酶分析验证先证者及家系其他成员基因突变情况。结果先证者RYR1基因第6724位碱基C突变为T（c．6724C〉T），所编码第2206位氨基酸由苏氨酸变为甲硫氨酸（p．T2206M），此突变在白种人已报道；先证者的4个子女中有2个为该错义突变携带者，为MH易感者。结论中国人MH易感者携带与白种人MH易感者相同的RYR1基因突变。

Objective To screen the ryanodine receptor type 1 （RYR1） gene in a Chinese pedigree with malignant hyperthermia（MH）. Methods Total genome was extracted conventionally from peripheral leucocytes of the proband and the other members of the family. In order to detect mutations in the RYR1 gene, part exons were amplified by polymerase chain reaction （PCR） and then subjected to automatic DNA sequencing. The detected mutation in the gene was confirmed in the proband and the other members of the family using Fok I restriction analysis. Results DNA sequencing of PCR-amplified fragments of the proband revealed c. 6724C 〉 T （p. T2206M）, a recurrent missense mutation which had been detected in Caucasian MH cases. Restriction analysis of all available family members showed that one daughter and one son of the 4 children of the proband were the missense mutation carriers, indicating that they were MH-suseeptible individuals. Conclusion The Chinese susceptible to MH carries the similar RYR1 gene mutation to the Caucasians susceptible to MH.