摘要
目的分析1个Ⅰ型肢根型点状软骨发育不良家系过氧化物酶生物合成因子7(peroxisomal biogenesis factor 7,PEX7)基因突变情况,探讨其致病原因。方法采集先证者留存羊水样本,先证者父母及其外祖父母、舅舅和50例体检健康者外周血,提取基因组DNA,进行全外显子组测序及生物信息学分析,采用Sanger测序法进行验证。结果先证者母亲及先证者外祖母存在PEX7基因c.45_52dupGGGACGCC位点杂合突变,先证者父亲存在PEX7基因c.527-1G>C剪接位点杂合突变,先证者存在PEX7基因c.45_52dupGGGACGCC位点和c.527-1G>C剪接位点复合杂合突变;先证者舅舅及先证者外祖父、50例体检健康者2个位点均为野生型。PEX7基因c.45_52dupGGGACGCC位点突变为已报道的致病性突变;c.527-1G>C剪接位点突变未报道,为可能致病性突变。结论 PEX7基因复合杂合突变可能是该家系Ⅰ型肢根型点状软骨发育不良患儿的致病原因。
Objective To analyze the peroxisomal biogenersis factor 7(PEX7) genetic mutation of a pedigree with rhizomelic chondrodysplasia punctata type Ⅰ and explore its pathogenic cause. Methods Amniotic fluid samples retained by the proband were collected, and genomic DNA was extracted from the peripheral blood of the proband’s parents, maternal grandparents and maternal uncle, as well as 50 healthy subjects. Whole-exome sequencing(WES) and bioinformatics analysis were performed, and Sanger sequencing was used for validation. Results The proband’s mother and maternal grandmother had c.45_52 dupGGGACGCC mutation of PEX7, the proband’s father had c.527-1 G>C splicing site mutation, and the proband had c. 45_52 dupGGGACGCC site and c. 527-1 G>C splicing site complex heterozygous mutation. These two loci of the proband’s maternal uncle and maternal grandfather as well as 50 healthy subjects were wild-type. The c.45_52 dupGGGACGCC mutation was reported pathogenic mutation;the c. 527-1 G>C splice site mutation had not been reported, indicating likely pathogenic mutation. Conclusion The complex heterozygous mutation of PEX7 is the likely pathogenic cause of fetuses with rhizomelic chondrodysplasia punctata type Ⅰ in the family.
作者
杨书雅
霍晓东
张颖
杨科
侯巧芳
YANG Shu-ya;HUO Xiao-dong;ZHANG Ying;YANG Ke;HOU Qiao-fang(Medical Genetics Institute,Henan University People’s Hospital,Henan Provincial People’s Hospital,Henan Key Laboratory of Genetic Diseases and Functional Genomics,Zhengzhou,Henan 450003,China;Department of Prenatal Diagnostic Center,Puyang Maternal and Child Health Hospital,Puyang,Henan 457099,China)
出处
《中华实用诊断与治疗杂志》
2022年第1期5-8,共4页
Journal of Chinese Practical Diagnosis and Therapy
基金
河南省医学科技攻关计划省部共建项目(201701016)。
