摘要
目的对一例孕18周既往生育过一名先天性甲状腺功能减退症(CH)患儿的孕妇实施遗传咨询及基因检测和介入性产前诊断,明确孕妇此次宫内胎儿的遗传信息和发育情况,对此次先证者新发现的DUOX2基因复合杂合突变进行临床遗传学分析,提高临床医生对该病认识,更好地学习DUOX2基因突变致甲状腺激素合成障碍引起CH,尽可能提高临床治疗效果改善患儿预后。方法抽取先证者及其父母外周血获取受检者基因组DNA进行全外显子组捕获和Sanger测序,获得的生物遗传学信息结果进行致病变异分析。对孕妇进行羊膜腔穿刺提取此次妊娠胎儿DNA进行单基因PCR检测。结果先证者染色体核型为46,XX。先证者携带DUOX2基因c.3478_3480del(p.Leu1160del)单一亮氨酸缺失及c.2654G>T(p.Arg885Leu)的复合杂合突变,分别来源于其父亲和母亲。其中父亲来源的c.3478_3480del(p.Leu1160del)为罕见的疑似致病变异,功能危害性预测为可能有害的突变;羊水穿刺结果提示:此次胎儿只携带DUOX2基因父源性c.3478_3480del(p.Leu1160del)单一亮氨酸杂合缺失。因DUOX2基因为常染色体隐性遗传模式夫妇双方选择继续妊娠。结论c.3478_3480del(p.Leu1160del)及c.2654G>T(p.Arg885Leu)复合杂合突变为先证者的致病性突变,随访至今先证者一切正常提示早期诊治的必要性。
Objective To provide genetic consulting and prenatal diagnosis for an 18-week pregnant woman who had previously given birth to a child with congenital hypothyroidism(CH),and to clarify the genetic information and development of the fetus in utero.Clinical genetic analysis of the newly discovered DUOX2 gene complex heterozygous mutation in the progenitor was conducted to improve clinicians’understanding of the disease,so as to better learn about DUOX2 gene mutation causing thyroid hormone synthesis disorder causing CH,and improve clinical treatment effect and prognosis of children as much as possible.Methods Peripheral blood of the proband and their parents was extracted to obtain their genomic DNA for whole exome capture and Sanger sequencing,and the results of the obtained biogenetic information were analyzed for pathogenic variation.Amniocentesis was performed on the pregnant woman to extract the fetal DNA of this pregnancy,and the obtained DNA was detected by single-gene PCR.Results The chromosome karyotype of the proband was 46,XX.The proband carried a single leucine deletion in the DUOX2 gene c.3478_3480del(p.Leu1160del)and a complex heterozygous mutation in the DUOX2 gene c.2654G>T(p.Arg885Leu),which were respectively derived from her father and mother,Paternal c.3478_3480del(p.Leu1160del)was a rare suspected pathogenic mutation,and its functional hazard was predicted to be possibly harmful.The results of amniocentesis suggested that the fetus carried a single leucine heterozygosity deletion of DUOX2 gene paternal c.3478_3480del(p.Leu1160del).Because the DUOX2 gene is an autosomal recessive inheritance pattern,the couple chooses to continue the pregnancy.Conclusion The hybrid mutation of c.3478_3480del(p.Leu1160del)and c.2654G>T(p.Arg885Leu)is the pathogenic mutation in the proband.All the proband has been normal so far,which suggests the necessity of early diagnosis and treatment.
作者
杨亚亚
王一丹
高健
YANG Yaya;WANG Yidan;GAO Jian(Reproductive Genetics Department,Hebei General Hospital,Shijiazhuang,Hebei 050051,China)
出处
《中国优生与遗传杂志》
2024年第6期1251-1254,共4页
Chinese Journal of Birth Health & Heredity
作者简介
通讯作者:高健,gaojian8703@163.com
