目的 面肩肱型肌营养不良症(facioscapulohumerial muscular dystrophy,FSHD)1型面肩肱肌营养不良致病基因组区域(4q35)的结构复杂性是导致无法常规产前基因诊断的主要制约性因素,探讨应用Karyomap基因芯片对FSHD1型进行产前诊断的可行性.方法 应用Karyomap基因芯片对5例已基因诊断确诊为FSHD1型的家系进行连锁分析,应用单分子光学图谱技术对2例胎儿样本进行基因诊断.结果 Karyomap基因芯片连锁分析显示5个家系中,3个胎儿携带先证者风险染色体,2个胎儿未携带先证者风险染色体.单分子光学图谱技术对家系1和家系2的胎儿的验证结果与Karyomap基因芯片结果一致.结论 Karyomap基因芯片技术可用于家系完整的FSHD1型的家系产前诊断,结合Bionano光学图谱技术进行D4Z4重复次数及4qA/B单元直接基因诊断可实现FSHD1型家系快速准确产前诊断.
Objective To assess the value of Karyomapping for the prenatal diagnosis of facioscapulohumerial muscular dystrophy type 1 (FSHD1).Methods Peripheral blood and chorionic villi samples were collected from five families affected with FSHD1.Linkage-based diagnosis was carried out by using the Karyomapping method.Diagnosis for two fetal samples was carried out with the next-generation optical mapping system.Results The results of karyomapping showed that three fetuses inherited the risky 4q35 region of the proband and two fetuses did not.The fetuses of families 1 and 2 received further diagnosis by the next-generation optical mapping system,and the results were consistent with those of karyomapping.Conclusion Karyomapping has enabled prenatal diagnosis for the five families affected with FSHD1.The method was faster and simpler compared with conventional strategies,though its feasibility still needs further validation.Since there were no SNP loci designed on the Karyomap chip for the DUX4 gene and its 3'flanking regions,misjudgment due to chromosomal recombination could not be completely eliminated.The accuracy of this method still needs further validation.