FOXRED1基因新突变鉴定分析和产前诊断

Identification and genetic analysis of novel mutations in FOXRED1 gene and prenatal diagnosis

目的对1个线粒体复合体Ⅰ缺乏症家系进行全外显子组基因测序分析,探讨FOXRED1基因突变情况,并进行产前诊断。方法采集表型正常、有3次不良生育史夫妻外周血,提取基因组DNA,进行全外显子组测序,筛选出致病性突变位点,采用Sanger测序法进行验证,对未报道的可疑致病突变进行生物信息学分析。明确致病突变后,于孕18周采集胎儿羊水进行产前诊断并随访。结果患者存在FOXRED1基因c.811-1G>C(splicing)杂合突变,患者丈夫存在FOXRED1基因c.1052G>A(p.R351H)杂合突变。FOXRED1基因c.811-1G>C(splicing)杂合突变为未报道的致病性突变,c.1052G>A(p.R351H)杂合突变为未报道的疑似致病性突变。Sanger测序结果显示,胎儿FOXRED1基因c.811-1G>C、c.1052G>A位点均为野生型。出生后随访6个月,婴儿发育正常,未见相关异常表型。结论FOXRED1基因c.811-1G>C(splicing)和c.1052G>A(p.R351H)复合杂合突变为患者多次不良生育的病因,产前诊断可降低该家系生育线粒体复合体Ⅰ缺乏症患儿的风险。

Objective To conduct whole exome sequencing analysis in a pedigree with mitochondrial complexⅠdeficiency,to investigate the mutation of FOXRED1 gene,and to make prenatal diagnosis.Methods Genomic DNA was extracted from the peripheral blood of a couple with normal phenotype and three times of abnormal pregnancy and birth for whole exome sequencing to select pathogenic mutations which were verified by Sanger sequencing.The unreported suspected pathogenic mutations were analyzed by bioinformatics.After defining the pathogenic mutation,the fetal amniotic fluid was collected at 18gestational weeks for prenatal diagnosis and follow-up.Results Heterozygous mutation of FOXRED1 gene c.811-1G>C(splicing)carried by the patient was the unreported pathogenic mutation,and the heterozygous mutation of c.1052G>A(p.R351H)carried by her husband was the unreported suspected pathogenic mutation.Sanger sequencing results showed that c.811-1G>C and c.1052G>A loci of FOXRED1 gene in fetus were wild type.After 6-month follow-up,the infant growth and development were normal,and no obvious abnormal phenotype was found.Conclusion The compound heterozygous mutation of FOXRED1 gene c.811-1G>C(splicing)and c.1052G>A(p.R351H)might be the genetic cause of many times of abnormal pregnancy and birth,and the prenatal diagnosis can reduce the risk of mitochondrial complexⅠdeficiency in this pedigree.