8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families.
8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families.
复制标题
DOI：
10.1186/1755-8166-3-3
复制
发表时间：
2010-02-18
影响因子：
1.3
通讯作者：
Maloney VK
中科院分区：
文献类型：
--
作者：
Barber JC;Bunyan D;Curtis M;Robinson D;Morlot S;Dermitzel A;Liehr T;Alves C;Trindade J;Paramos AI;Cooper C;Ocraft K;Taylor EJ;Maloney VK
8p23.1重复综合征和8p23.1防御蛋白基因簇的拷贝数变异在细胞遗传学上是不可区分的，但在分子水平上是不同的。据我们所知，8p23.1重复综合征在产前诊断中只被描述过一次，我们报告了我们在产前诊断中确定的另外四个明显重复的经验。在每个病例中，使用常规g带细胞遗传学检测8p23.1波段的额外物质。根据是否只有DNA（病例1和4）或细胞遗传学制剂（病例2和3）可从来源实验室获得，使用多重连接依赖探针扩增（MLPA）或荧光原位杂交（FISH）。病例1的重复程度采用比较基因组杂交（CGH）阵列进行回顾性测定。发现8p23.1重复综合征3例（病例1 ~ 3）。其中两个是新生的，并继续足月，第三个是父系遗传的复制，由于先前的孩子患有精神运动迟缓和8p23.1复制综合征而终止。病例1被确定为左心发育不全，但病例2和病例3分别在确定为高龄产妇后发现室间隔和室间缺陷。相比之下，病例4是母系传递的防御蛋白簇拷贝数变异，结果正常。我们的数据强调需要使用FISH、MLPA或阵列CGH来区分防御蛋白簇的8p23.1重复和拷贝数变化。在三例重复8p23.1基因的妊娠中，只有一例通过超声检查发现了心脏缺陷，但在怀孕21至22周时，三例中有两例可以看到心脏缺陷。我们的研究结果进一步证明，GATA4转录因子的缺失和重复都可以导致多种外显率和表达性不同的锥形心脏缺陷。
The 8p23.1 duplication syndrome and copy number variation of the 8p23.1 defensin gene cluster are cytogenetically indistinguishable but distinct at the molecular level. To our knowledge, the 8p23.1 duplication syndrome has been described at prenatal diagnosis only once and we report our experience with four further apparent duplications ascertained at prenatal diagnosis. Additional material at band 8p23.1 was detected using conventional G-banded cytogenetics in each case. Multiplex Ligation-dependent Probe Amplification (MLPA) or Fluorescence In Situ Hybridisation (FISH) were used depending on whether only DNA (Cases 1 and 4) or cytogenetic preparations (Cases 2 and 3) were available from the laboratory of origin. The extent of the duplication in Case 1 was retrospectively determined using array Comparative Genomic Hybridisation (array CGH). Three cases of 8p23.1 duplication syndrome were found (Cases 1 to 3). Two were de novo and continued to term and the third, a paternally transmitted duplication, was terminated because of a previous child with psychomotor delay and 8p23.1 duplication syndrome. Case 1 was ascertained with a hypoplastic left heart but the ventricular septal and interventricular defects, in Cases 2 and 3 respectively, were found after ascertainment for advanced maternal age. By contrast, case 4 was a maternally transmitted copy number variation of the defensin cluster with normal outcome. Our data underline the need to differentiate 8p23.1 duplications from copy number variation of the defensin cluster using FISH, MLPA or array CGH. Cardiac defects were ascertained by ultrasound in only one of the three duplication 8p23.1 pregnancies but were visible in two of the three at 21 to 22 weeks gestation. Our results provide further evidence that both deletion and duplication of the GATA4 transcription factor can give rise to a variety of conotruncal heart defects with variable penetrance and expressivity.
登录
查看更多内容
影响因子：
9.8
作者：
Hollox, EJ;Armour, JAL;Barber, JCK
通讯作者：
Barber, JCK
影响因子：
9.8
作者：
Fellermann, Klaus;Stange, Daniel E.;Stange, Eduard F.
通讯作者：
Stange, Eduard F.
影响因子：
4
作者：
Okubo, A;Miyoshi, O;Matsumoto, N
通讯作者：
Matsumoto, N
影响因子：
2
作者：
Paez, Marco T.;Yamamoto, Toshiyuki;Matsuoka, Rumiko
通讯作者：
Matsuoka, Rumiko
影响因子：
2
作者：
Shimokawa, O;Miyake, N;Matsumoto, N
通讯作者：
Matsumoto, N