Genotype and cardiovascular phenotype correlations with TBX1 in 1,022 velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients.
Genotype and cardiovascular phenotype correlations with TBX1 in 1,022 velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients.
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基因型和心血管表型与TBX1的相关性在1,022个天线 - 核对面/digeorge/22q11.2缺失综合征患者中。
DOI：
10.1002/humu.21568
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发表时间：
2011-11
期刊：
影响因子：
3.9
通讯作者：
Morrow, Bernice
中科院分区：
文献类型：
--
作者：
Guo, Tingwei;McDonald-McGinn, Donna;Blonska, Anna;Shanske, Alan;Bassett, Anne S.;Chow, Eva;Bowser, Mark;Sheridan, Molly;Beemer, Frits;Devriendt, Koen;Swillen, Ann;Breckpot, Jeroen;Digilio, Maria C.;Marino, Bruno;Dallapiccola, Bruno;Carpenter, Courtney;Zheng, Xin;Johnson, Jacob;Chung, Jonathan;Higgins, Anne Marie;Philip, Nicole;Simon, Tony J.;Coleman, Karlene;Heine-Suner, Damian;Rosell, Jordi;Kates, Wendy;Devoto, Marcella;Goldmuntz, Elizabeth;Zackai, Elaine;Wang, Tao;Shprintzen, Robert;Emanuel, Beverly;Morrow, Bernice
TBX 1编码一个T-box转录因子，其单倍不足是导致腭-心-面/DiGeorge/22q11.2缺失综合征（22 q11 DS）患者身体畸形的主要原因。这些患者的心血管畸形是高度可变的，这就提出了一个问题，即22q11.2剩余等位基因上TBX 1基因座的DNA变异是否可能是原因。为了验证这一点，需要大样本量。对360例22 q11 DS患者的TBX 1基因进行测序。罕见和常见的变化被确定。我们没有检测到在那些有或没有先天性心脏缺陷的罕见SNP数量的富集。一个例外是，与右侧主动脉弓或永存动脉干患者相比，心脏解剖正常的患者中非常罕见的SNP数量增加，这表明SNP对这些表型富集组具有潜在的保护作用。选择9个常见的SNP（MAF >0.05），并用于对整个队列的1，022名22 q11 DS受试者进行基因分型。我们没有发现常见的SNPs或单倍型与心血管表型之间的相关性。这项工作表明，TBX 1中常见的DNA变异不能解释22 q11 DS患者中可变的心血管表达，这意味着在22q11.2或基因组其他地方的其他基因中存在修饰符。
Haploinsufficiency of TBX1, encoding a T-box transcription factor, is largely responsible for the physical malformations in velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome (22q11DS) patients. Cardiovascular malformations in these patients are highly variable, raising the question as to whether DNA variations in the TBX1 locus on the remaining allele of 22q11.2, could be responsible. To test this, a large sample size is needed. The TBX1 gene was sequenced in 360 consecutive 22q11DS patients. Rare and common variations were identified. We did not detect enrichment in rare SNP number in those with or without a congenital heart defect. One exception was that there was increased number of very rare SNPs between those with normal heart anatomy compared to those with right-sided aortic arch or persistent truncus arteriosus, suggesting potentially protective roles in the SNPs for these phenotype enrichment groups. Nine common SNPs (MAF >0.05) were chosen and used to genotype the entire cohort of 1,022 22q11DS subjects. We did not find a correlation between common SNPs or haplotypes and cardiovascular phenotype. This work demonstrates that common DNA variations in TBX1 do not explain variable cardiovascular expression in 22q11DS patients, implicating existence of modifiers in other genes on 22q11.2 or elsewhere in the genome.
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有或没有22Q11.2缺失综合征的个体中TBX1中的单核苷酸多态性发现。
DOI：
10.1002/bdra.20604
发表时间：
2010-01
期刊：
Birth defects research. Part A, Clinical and molecular teratology
影响因子：
--
作者：
Heike CL;Starr JR;Rieder MJ;Cunningham ML;Edwards KL;Stanaway IB;Crawford DC
通讯作者：
Crawford DC
影响因子：
11.8
作者：
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通讯作者：
Imamoto, A
影响因子：
9.8
作者：
Edelmann, L;Pandita, RK;Morrow, BE
通讯作者：
Morrow, BE
影响因子：
5.7
作者：
Griffin, Helen R.;Toepf, Ana;Goodship, Judith A.
通讯作者：
Goodship, Judith A.
影响因子：
9.8
作者：
Li, Bingshan;Leal, Suzanne M.
通讯作者：
Leal, Suzanne M.