原发性肉碱缺乏症一家系的SLC22A5基因突变检测与产前诊断

Genetic and prenatal diagnosis for a Chinese family with primary carnitine deficiency

目的对1例原发性肉碱缺乏症患儿及其家系进行SLC22A5基因突变检测，确定其突变位点，为家系提供遗传咨询和产前诊断。方法收集该家系成员的外周血标本及先证者母亲的羊水标本，提取基因组DNA，运用Sanger法对家系中各成员进行SLCY2A5基因lO个外显子的直接测序，并对羊水标本行常规染色体核型分析及应用多重连接依赖探针扩增技术（multiplex ligation-dependent probe amplificating，MLPA）检测常见染色体微缺失综合征。结果Sanger法DNA测序检测出该家系中先证者携带sLC22A5基因12．760C〉T（P．R254X）纯合突变，先证者父亲、母亲和姐姐均携带SLC22A5基因e．760C〉T（P．R254X）杂合突变。先证者母亲羊水标本也检测出SLC22A5基因c．760C〉T（P．R254X）杂合突变，羊水染色体核型分析及MLPA检测均无异常发现。结论SLC22A5基因c．760C〉T突变可能是本家系中先证者患原发性肉碱缺乏症的致病突变，Sanger测序等技术可为原发性肉碱缺乏症家系提供遗传咨询和产前诊断服务。

Objective To identify potential mutation of SLC22A5 gene in a 5-month-old boy affected with primary carnitine deficiency and provide genetic counseling and prenatal diagnosis for the members of his family. Methods DNA was extracted from peripheral blood samples derived from the proband, his parents and elder sister, as well as amniotic fluid from his pregnant mother. All of the 10 exons of the SLC22A5 gene were amplified by PCR and subjected to Sanger sequencing. The amniotic fluid sample was also subjected to C-banded karyotyping and multiplex ligation-dependent probe amplification （MLPA）. Results A homozygous mutation c. 760C〉T （p. R254X） of the SLC22A5 gene was detected in the proband. Heterozygous mutation c. 760C〉T （p. R254X） was also found in other family members including the fetus. The karyotyping and chromosomal microdeletion testing for the amniotic fluid sample were both normal. Conclusion The newly identified homozygous nonsense c. 760C〉T （p. R254X） mutation of the SLC22A5 gene probably underlies the primary carnitine deficiency of the proband. Genetic counseling and prenatal diagnosis have been provided for this family.