Cao Qinying, Mu Weihong, Sun Donglan, Zhu Junzhen, Ge Jun, Peng Yuanyuan, Zhang Jing
The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 May 10;38(5):450-453. doi: 10.3760/cma.j.cn511374-20200319-00181.
To screen for mutations of fragile X mental retardation 1 (FMR1) gene during early and middle pregnancy and provide prenatal diagnosis for those carrying high-risk CGG trinucleotide expansions.
Peripheral blood samples of 2316 pregnant women at 12 to 21(+6) gestational weeks were collected for the extraction of genomic DNA. CGG repeats of the FMR1 gene were detected by fluorescence PCR and capillary electrophoresis. Genetic counseling and prenatal diagnosis were provided for 3 women carrying the premutations.
The carrier rate of CGG repeats of the FMR1 gene was 1 in 178 for the intermediate type and 1 in 772 for the premutation types. The highest frequency allele of CGG was 29 repeats, which accounted for 49.29%, followed by 30 repeats (28.56%) and 36 repeats (8.83%). In case 1, the fetus had a karyotype of 45,X, in addition with premutation type of CGG expansion of the FMR1 gene. Following genetic counseling, the couple chose to terminate the pregnancy through induced labor. The numbers of CGG repeats were respectively 70/- and 29/30 for the husband and wife. In case 2, amniocentesis was performed at 20 weeks of gestation. The number of CGG repeats of the FMR1 gene was 29/-. No abnormality was found in the fetal karyotype and chromosomal copy number variations. The couple chose to continue with the pregnancy. Case 3 refused prenatal diagnosis after genetic counseling and gave birth to a girl at full term, who had a birth weight of 2440 g and no obvious abnormality found during follow-up.
Pregnant women should be screened for FMR1 gene mutations during early and middle pregnancy, and those with high-risk CGG expansions should undergo prenatal diagnosis, genetic counseling and family study.
筛查早孕期和中孕期脆性X智力低下1（FMR1）基因的突变情况，为携带高风险CGG三核苷酸重复扩增的孕妇提供产前诊断。
收集2316例孕12至21⁺⁶周孕妇的外周血样本，提取基因组DNA。采用荧光PCR和毛细管电泳检测FMR1基因的CGG重复序列。为3例携带前突变的孕妇提供遗传咨询和产前诊断。
FMR1基因CGG重复序列的中间型携带率为1/178，前突变型为1/772。CGG的最高频率等位基因是29次重复，占49.29%，其次是30次重复（28.56%）和36次重复（8.83%）。病例1中，胎儿核型为45,X，同时伴有FMR1基因CGG扩增的前突变型。经过遗传咨询，这对夫妇选择引产终止妊娠。丈夫和妻子的CGG重复次数分别为70/ -和29/30。病例2在妊娠20周时进行了羊水穿刺。FMR1基因的CGG重复次数为29/ -。胎儿核型和染色体拷贝数变异未发现异常。这对夫妇选择继续妊娠。病例3在遗传咨询后拒绝产前诊断，足月分娩一女婴，出生体重2440 g，随访期间未发现明显异常。
早孕期和中孕期孕妇应进行FMR1基因突变筛查，携带高风险CGG扩增的孕妇应接受产前诊断、遗传咨询和家系研究。
