产前诊断先天性心血管畸形胎儿TUPLE1基因缺失的研究
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摘要
目的:对先天性心血管畸形胎儿中染色体22q11位点TUPLE1基因微缺失进行产前诊断的研究。方法:选取经产前超声心动图诊断为胎儿先天性心血管畸形且排除染色体核型异常病例52例,其中单纯心血管畸形44例,同时合并心外畸形8例。产前经脐带血穿刺留取胎儿血,应用FISH技术检测TUPLE1基因缺失。选取同期30例正常新生儿脐带血作为对照。结果:正常新生儿组与先天性心血管畸形胎儿组TUPLE1缺失率分别为0%和5.77%(3/52)。单纯心血管畸形与合并心外畸形胎儿组的TUPLE1缺失率分别为2.27%(1/44)及25.00%(2/8)。结论:在先天性心血管畸形胎儿中TUPLE微缺失有一定的发生率,产前对先天性心血管畸形患儿进行TUPLE1基因微缺失检测可以明确先心病发病机制,也有助于22q11微缺失综合征的优生优育遗传咨询。
Objective: To conduct prenatal diagnosis for TUPLE1 gene microdeletion in chromosomal 22q11 locus of fetuses with congenital cardiovascular malformations. Methods: A total of 52 fetuses with congenital cardiovascular malformations diagnosed by prenatal ultrasonic cardiography were selected,including 44 fetuses with simple cardiovascular malformations and 8 fetuses with cardiovascular malformations combined with extracardiac malformations. Umbilical cord blood samples were obtained before birth,TUPLE1 gene microdeletion was detected by FISH,30 normal fetuses were selected as control group. Results: The incidence rates of TUPLE1 gene microdeletion in control group and congenital cardiovascular malformations group were 0% and 5. 77%( 3 /52),respectively; the incidence rates of TUPLE1 gene microdeletion in fetuses with simple cardiovascular malformations and fetuses with cardiovascular malformations combined with extracardiac malformations were 2. 27%( 1 /44) and 25. 00%( 2 /8),respectively. Conclusion: TUPLE1 gene microdeletion exists in fetuses with congenital cardiovascular malformations. Prenatal diagnosis of TUPLE gene microdeletion in fetuses with congenital cardiovascular malformations can confirm the mechanism of congenital heart disease and be helpful to genetic counseling of eugenics in fetuses with 22q11 microdeletion syndrome.
Objective: To conduct prenatal diagnosis for TUPLE1 gene microdeletion in chromosomal 22q11 locus of fetuses with congenital cardiovascular malformations. Methods: A total of 52 fetuses with congenital cardiovascular malformations diagnosed by prenatal ultrasonic cardiography were selected,including 44 fetuses with simple cardiovascular malformations and 8 fetuses with cardiovascular malformations combined with extracardiac malformations. Umbilical cord blood samples were obtained before birth,TUPLE1 gene microdeletion was detected by FISH,30 normal fetuses were selected as control group. Results: The incidence rates of TUPLE1 gene microdeletion in control group and congenital cardiovascular malformations group were 0% and 5. 77%( 3 /52),respectively; the incidence rates of TUPLE1 gene microdeletion in fetuses with simple cardiovascular malformations and fetuses with cardiovascular malformations combined with extracardiac malformations were 2. 27%( 1 /44) and 25. 00%( 2 /8),respectively. Conclusion: TUPLE1 gene microdeletion exists in fetuses with congenital cardiovascular malformations. Prenatal diagnosis of TUPLE gene microdeletion in fetuses with congenital cardiovascular malformations can confirm the mechanism of congenital heart disease and be helpful to genetic counseling of eugenics in fetuses with 22q11 microdeletion syndrome.
引文
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2 Momma K.Cardiovascular anomalies associated with chromosome 22q11.2 deletion syndrome[J].Am J Cardiol,2010,105(11):1617-1624.
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6 Park IS,Ko JK,Kim YH,et al.Cardiovascular anomalies in patients with chromosome 22q11.2 deletion:a Korean multicenter study[J].Int J Cardiol,2007,114(2):230-235.
7 孙晓燕,王云英,瓮占平,等.TUPLE1基因缺失在先天性心脏病发病机制中作用的研究[J].中国优生与遗传杂志,2013,21(2):132.
8 Vieira TP,Monteiro FP,Sgardioli IC,et al.Clinical features in patients with 22q11.2 deletion syndrome ascertained by palatal abnormalities[J].Cleft Palate Craniofac J,2014 May7 .[Epub ahead of print]
9 秦玉峰,杨建滨,解春红,等.染色体22q11微缺失综合征的临床表现与荧光原位杂交诊断结果[J].中华医学遗传学杂志,2007,24(3),284-287.
10 王凤羽,马林先,李聪敏,等.先天性心脏病患儿22q11微缺失的临床研究.中国计划生育学杂志,2012,20(2):109-112.
11 Bachman KK,Deward SJ,Chrysostomou C,et al.Array CGH as a first-tier test for neonates with congenital heart disease[J].Cardiol Young,2013,6:1-8.
12 Lee MY,Won HS,Baek JW,et al.Variety of prenatally diagnosed congenital heart disease in 22q11.2 deletion syndrome[J].Obstet Gynecol Sci,2014,57(1):11-6.
2 Momma K.Cardiovascular anomalies associated with chromosome 22q11.2 deletion syndrome[J].Am J Cardiol,2010,105(11):1617-1624.
3 Carlson C,Sirotkin H,Pandita R,et al.Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients[J].Am J Hum Genet,1997,61(3):620-629.
4 Halford S,Wilson DI,Daw SC,et al.Isolation of a gene expressed during early embryogenesis from the region of 22q11commonly deleted in DiGeorge syndrome[J].Hum Mol Genet,1993,2(10):1577-1582.
5 Roberts C,Sutherland HF,Farmer H,et al.Targeted mutagenesis of the Hira gene results in gastrulation defects and patterning abnormalities of mesoendodermal derivatives prior to early embryonic lethality[J].Mol Cell Biol,2002,22(7):2318-2328.
6 Park IS,Ko JK,Kim YH,et al.Cardiovascular anomalies in patients with chromosome 22q11.2 deletion:a Korean multicenter study[J].Int J Cardiol,2007,114(2):230-235.
7 孙晓燕,王云英,瓮占平,等.TUPLE1基因缺失在先天性心脏病发病机制中作用的研究[J].中国优生与遗传杂志,2013,21(2):132.
8 Vieira TP,Monteiro FP,Sgardioli IC,et al.Clinical features in patients with 22q11.2 deletion syndrome ascertained by palatal abnormalities[J].Cleft Palate Craniofac J,2014 May7 .[Epub ahead of print]
9 秦玉峰,杨建滨,解春红,等.染色体22q11微缺失综合征的临床表现与荧光原位杂交诊断结果[J].中华医学遗传学杂志,2007,24(3),284-287.
10 王凤羽,马林先,李聪敏,等.先天性心脏病患儿22q11微缺失的临床研究.中国计划生育学杂志,2012,20(2):109-112.
11 Bachman KK,Deward SJ,Chrysostomou C,et al.Array CGH as a first-tier test for neonates with congenital heart disease[J].Cardiol Young,2013,6:1-8.
12 Lee MY,Won HS,Baek JW,et al.Variety of prenatally diagnosed congenital heart disease in 22q11.2 deletion syndrome[J].Obstet Gynecol Sci,2014,57(1):11-6.