摘要
目的分析7例低深度全基因组测序(copy number variation sequencing,CNV-seq)检出仅涉及NRXN1基因的2p16.3杂合缺失胎儿的遗传学检查结果、拷贝数变异(copy number variation,CNV)来源及妊娠结局,为产前诊断和遗传咨询提供依据。方法7例产前诊断样本均通过CNV-seq检测发现2p16.3杂合缺失,进一步通过实时荧光定量PCR(quantitative real-time PCR,qPCR)进行验证,明确涉及的NRXN1基因缺失的具体区域,并对CNV进行父母验证和妊娠结局的随访。结果在16502例样本中共检出7例胎儿染色体2p16.3区存在120~900 kb的微缺失,发生率为0.424‰。该区域主要位于2号染色体的50200000-51880000位置,仅覆盖了NRXN1基因。qPCR验证了7例胎儿的CNV,其中2例涉及NRXN1基因第1~6外显子杂合缺失,1例涉及第1~19外显子杂合缺失,1例涉及第19~22外显子杂合缺失,3例涉及第6~7内含子杂合缺失。亲代验证发现父源性1例,母源性1例,新发2例,其余3例拒绝亲代验证。经随访,除1例引产,1例尚未出生外,其余5例均健康出生,年龄5个月~3岁,均未发现NRXN1相关的精神发育异常。结论CNV-seq检出7例胎儿涉及NRXN1基因的2p16.3杂合缺失,经qPCR验证NRXN1基因的具体缺失位置,通过结合CNV来源、家系分析以及妊娠结局,对每个家庭进行了个体化的遗传咨询及生育指导。
Objective To summarize the genetic diagnosis,low-depth copy number variation sequencing(CNV-Seq)and prenatal finding in 7 fetuses with 2p16.3 deletions only involving the NRXN1 gene.Methods The 7 fetuses have all been found to have loss of heterozygosity at 2p16.3 by CNV-seq,which were verified by quantitative real-time PCR(qPCR).Specific regions of NRXN1 gene deletions were identified,and the CNVs were verified in their parents.Outcome of the pregnancies were followed up.Results Among 16502 prenatal samples,7 fetuses were found to harbor a 120 kb~900 kb microdeletion in the 2p16.3 region,which yielded a prevalence of 0.424‰.The deleted region mainly involved 50200000-51880000 positions of chromosome 2 and involved only the NRXN1 gene.All of the 7 fetal CNVs were confirmed by qPCR,including 2 cases with heterozygous deletion of exons 1 to 6,1 with heterozygous deletion of exons 1 to 19,1 with heterozygous deletion of exons 19 to 22,and 3 with heterozygous deletion of introns 6 to 7 of the NRXN1 gene.Verification in the parents had found that one deletion was inherited from the father,1 was from the mother,2 cases were de novo in origin,whilst the remaining 3 had refused parental verification.After genetic counseling,one couple had elected induced abortion,1 case has not been born yet,whilst the other 5 cases were born healthy.Follow up had identified no mental abnormalities among the children.Conclusion Seven fetuses with heterozygous 2p16.3 deletions only involving the NRXN1 gene were detected by CNV-seq.The specific deletion of the NRXN1 gene was verified by qPCR.Prenatal genetic counseling and fertility guidance has been provided to the particular family by combining the results of CNV testing,pedigree analysis and pregnancy outcome.
作者
王丽霞
时盼来
任化楠
薛淑媛
孔祥东
Wang Lixia;Shi Panlai;Ren Hua′nan;Xue Shuyuan;Kong Xiangdong(Prenatal Diagnosis Center,Urumqi Maternal and Child Health Care Hospital,Urumqi,Xinjiang 830000,China;Genetic and Prenatal Diagnosis Center,Department of Obstetrics and Gynecology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2022年第11期1200-1204,共5页
Chinese Journal of Medical Genetics
