COL1A2基因生殖腺嵌合变异的分析  

Analysis of a case with gonadal mosaicism for COL1A2 variant

作　　者：朱海燕 陈媛媛 王丽丽 王伟周 贺声 Zhu Haiyan;Chen Yuanyuan;Wang Lili;Wang Weizhou;He Sheng(Prenatal Diagnosis Center,Department of Gynecology and Obstetrics,the Sixth Medical Center of PLA General Hospital,Beijing 100048,China;Department of Ultrasonography,the Sixth Medical Center of PLA General Hospital,Beijing 100048,China)

机构地区：[1]中国人民解放军总医院第六医学中心妇产科产前诊断中心,北京100048 [2]中国人民解放军总医院第六医学中心超声科,北京100048

出　　处：《中华医学遗传学杂志》2020年第5期523-526,共4页Chinese Journal of Medical Genetics

摘　　要：目的对1例亲代表型正常但反复妊娠骨骼发育异常胎儿(可疑成骨不全)的家系进行遗传学分析,探讨胎儿的发病原因。方法对胎儿标本及亲代DNA进行全外显子组测序(whole exome sequencing,WES),针对WES检测到的阳性位点进行Sanger测序验证。采集提取丈夫精液与单精子DNA,对致病位点进行PCR扩增并Sanger测序。结果WES检测到胎儿COL1A2基因c.1378G>A(p.G460S)杂合变异,为致病变异,夫妻双方外周血DNA均未检测到该变异。精液DNA检测到该位点野生型与变异型序列,在15个精子中有4个检测到该位点变异。结论为1例骨骼发育异常的胎儿明确了成骨不全的遗传学诊断。亲代的生殖腺嵌合是该家系反复妊娠骨骼发育异常胎儿的原因。在临床遗传咨询过程中,对于表型和和基因型均正常但反复生育或妊娠相同异常表型后代的案例,需要考虑到生殖腺嵌合的可能原因。Objective To explore the genetic basis for a couple with normal phenotype but repeated pregnancies with fetuses affected by osteogenesis imperfecta.Methods Whole exome sequencing(WES)was carried out on fetal specimens and parental DNA to detect potential pathologic variants.Suspected variants were verified by Sanger sequencing.Semen sample of the husband was collected for the extraction of genome DNA,and whole genome amplification(WGA)was performed for single sperms isolated from the sample.Results WES has identified a heterozygous c.1378G>A(p.G460S)variant of the COL1A2 gene in the fetus,which was predicted to be pathogenic but not detected in peripheral blood samples of both husband and wife.The heterozygotic variant was detected in semen DNA from the husband.Among 15 spermatozoa,4 were found to harbor the variant.Conclusion The fetus was diagnosed with osteogenesis imperfecta,and the gonadal mosaicism probably accounted for the repeated abnormal pregnancies.Possibility of gonadal mosaicism should be considered when counseling couples with normal phenotype and genotype but recurrent abnormal pregnancies and/or births of children with similar phenotypes and genetic variants.

关 键 词：成骨不全 COL1A2基因 生殖腺嵌合 变异 表型 基因型 

分 类 号：R714[医药卫生—妇产科学]