一个X连锁低磷血症家系的PHEX基因变异分析及产前诊断

Analysis of PHEX gene variant and prenatal diagnosis for a Chinese pedigree affected with X-linked hypophosphatemia

目的对1个X连锁低磷血症(X-linked hypophosphatemia,XLH)家系进行致病原因分析,明确其致病变异,为家系遗传咨询及产前诊断提供帮助。方法应用全外显子测序技术对先证者及其父母进行变异筛查,发现磷酸盐调节基因(phosphate regulating gene with homologies to endopeptidases on the X chromosome,PHEX)可疑致病位点后,用Sanger测序技术对该家系所有成员和100名正常对照进行变异验证,并对先证者胎儿抽取绒毛标本进行产前诊断。结果先证者及家系中所有患者均携带PHEX基因c.1256G>A(p.Gly419Glu)变异,而家系中正常成员和100名正常对照中均未检测到该变异。产前诊断结果提示胎儿也携带PHEX基因c.1256G>A(p.Gly419Glu)杂合变异。结论PHEX基因c.1256G>A(p.Gly419Glu)变异是该家系的致病原因,拓宽了PHEX基因变异谱。

Objective To detect pathological variant in a Chinese pedigree affected with X-linked hypophosphatemia(XLH).Methods Whole-exome sequencing was carried out to screen genetic variants in the proband and her parents.Candidate variant of the phosphate regulating gene with homologies to endopeptidases on the X chromosome(PHEX)was verified by Sanger sequencing of all members of the pedigree and the 100 healthy controls.Prenatal diagnosis was carried out on chorionic villi sample derived from the fetus of the proband.Results A c.1256G>A(p.Gly419Glu)variant was identified in the PHEX gene of the proband and all other patients from this pedigree.The same variant was not found among healthy members from this pedigree and the 100 healthy controls.Prenatal diagnosis suggested that the fetus also carried the c.1256G>A(p.Gly419Glu)variant.Conclusion The c.1256G>A(p.Gly419Glu)variant of the PHEX gene probably underlay the pathogenesis of XLH in this family.Discovery of the novel variant has enriched the mutational spectrum of the PHEX gene.