摘要
目的总结22个单基因遗传性骨病家系的产前诊断特点, 探讨产前分子诊断技术的应用价值, 切实阻断遗传性疾病的遗传链。方法回顾性分析2014年1月至2021年7月就诊于本院骨质疏松和骨病专科门诊的22个单基因遗传性骨病家系的产前分子诊断结果。结果在22个家系中, X连锁低磷佝偻病家系10例, 均为PHEX基因突变, 共检测到胎儿突变8例;骨硬化症家系6例, 其中CLCN7基因突变3例, TCIRG1基因突变2例, CTSK基因突变1例, 共检测到患胎2例, 携带者1例;成骨不全症4例, COL1A1基因突变2例, COL1A2和SERPINF1基因突变各1例, 共检测到患胎1例, 携带者1例;骨关节炎伴轻度软骨发育不良1例, 由COL2A1基因突变所致, 胎儿检测到该致病突变;低磷酸酶症1例, 为ALPL基因突变, 胎儿未检测到该致病突变。截止随访时间, 12例患胎均终止妊娠, 剩余10例胎儿除了1例仍在妊娠中, 其余均已出生, 健康状况良好。结论产前分子诊断可以在妊娠早、中期明确胎儿是否携带遗传变异。对于符合孟德尔分离定律的单基因遗传性骨病, 可以通过推算子代再发风险的概率决定是否进行产前诊断。另外, 对于子代出现新发突变的家系, 需要注意亲代是否存在嵌合突变。
Objective To evaluate the clinical value of prenatal molecular diagnostic technology in preventing hereditary diseases through analysis of prenatal diagnostic characteristics in 22 monogenic skeletal disorders pedigrees.Methods This study retrospectively analyzed prenatal molecular diagnostic results of 22 pedigrees with monogenic skeletal disorders who were admitted to Department of Osteoporosis and Bone Diseases in our hospital from January 2014 to July 2021.Results Among 22 pedigrees,there were 10 pedigrees with X-linked hypophosphatemic rickets due to PHEX gene mutations,in which 8 fetuses were found to carry pathogenic variants;6 pedigrees with osteopetrosis,including 3 cases of CLCN7 gene mutation,2 TCIRG1 gene mutation,and 1 CTSK gene mutation,were detected to have 2 affected fetuses and 1 carrier.There were 4 cases of osteogenesis imperfecta,including 2 cases of COL1A1 gene mutation,1 case of COL1A2 gene mutation,and 1 case of SERPINF1 gene mutation,in which 1 affected fetus and 1 carrier were found;only one case of osteoarthritis with mild chondrodysplasia caused by COL2A1 gene mutation was found to harbor pathogenic variant in fetus;1 case of hypophosphatasia due to ALPL gene mutation was not detected to carry pathogenic variant in fetus.By the time of follow-up,all 12 affected fetuses were terminated,and the remaining 10 fetuses except for one case still in pregnancy were born in good condition.Conclusion Prenatal molecular diagnosis may confirm whether the fetus carries pathogenic variants at the first and second trimesters.For monogenic skeletal disorders that comply with Mendel′s law of separation,prenatal diagnosis can be determined by calculating the probability of recurrence of offspring.In addition,for families with de novo mutations in the offspring,it is necessary to pay attention to whether there are mosaic mutations in the parents.
作者
梅亚曌
傅文贞
岳华
汪纯
胡伟伟
顾洁梅
李珊珊
张浩
章振林
Mei Yazhao;Fu Wenzhen;Yue Hua;Wang Chun;Hu Weiwei;Gu Jiemei;Li Shanshan;Zhang Hao;Zhang Zhenlin(Shanghai Clinical Research Center of Bone Diseases,Department of Osteoporosis and Bone Diseases,Shanghai Jiao Tong University Affiliated Shanghai Sixth People′s Hospital,Shanghai 200223,China)
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2022年第7期595-600,共6页
Chinese Journal of Endocrinology and Metabolism
基金
国家重点研发计划(2018YFA0800801)
国家自然科学基金(81870618)
上海市申康医院发展中心新兴前沿技术联合攻关项目(SHDC12018120)。
关键词
单基因遗传性骨病
遗传咨询
产前诊断
羊膜腔穿刺术
嵌合突变
Monogenic skeletal disorders
Genetic counseling
Prenatal diagnosis
Amniocentesis
Mosaic mutation
