Molecular detection of microscopic and submicroscopic deletions associated with Miller-Dieker syndrome.
Molecular detection of microscopic and submicroscopic deletions associated with Miller-Dieker syndrome.
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发表时间：
1988-11
影响因子：
9.8
通讯作者：
P. Vantuinen;W. Dobyns;D. C. Rich;Kim M. Summers;Terence J. Robinson;Y. Nakamura;D. Ledbetter
中科院分区：
文献类型：
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作者：
P. Vantuinen;W. Dobyns;D. C. Rich;Kim M. Summers;Terence J. Robinson;Y. Nakamura;D. Ledbetter
Miller-Dieker综合征（MDS）是一种表现为严重脑畸形无脑畸形（“光滑脑”）的疾病，在大多数情况下是由17号染色体远端短臂的染色体微缺失引起的。使用人类17号染色体特异性DNA探针，我们已经开始了MDS关键区域的分子解剖。为了将克隆的DNA序列定位于MDS关键区域，构建了人-啮齿动物体细胞杂交组，其包括含有来自具有各种大小缺失的三个MDS患者的异常染色体17的杂交体。三个基因（肌球蛋白重链2，肿瘤抗原p53和RNA聚合酶II）以前映射到17 p被排除在MDS缺失区，因此不太可能在其发病机制中发挥作用。相比之下，三个高度多态性的匿名探针，YNZ22.1（D17 S5），YNH 37.3（D17 S28），和144-D 6（D17 S34），删除在每四个患者的可见缺失，包括一个与环状染色体17，删除了一部分的单一端粒前中期子带p13.3。在两个MDS患者与正常染色体，体细胞杂交，RFLP，和光密度研究的组合证明删除YNZ22.1和YNH 37.3在父系衍生的17的两个患者，其中一个也删除了144-D 6。结果表明，MDS可能是由亚显微缺失引起的，并提出了所有MDS患者将被证明在分子水平上具有缺失的可能性。这两个探针位于小于3，000 kb的关键区域内，并构成了分离MDS中严重脑发育不良相关基因的潜在起点。
Miller-Dieker syndrome (MDS), a disorder manifesting the severe brain malformation lissencephaly ("smooth brain"), is caused, in the majority of cases, by a chromosomal microdeletion of the distal short arm of chromosome 17. Using human chromosome 17-specific DNA probes, we have begun a molecular dissection of the critical region for MDS. To localize cloned DNA sequences to the MDS critical region, a human-rodent somatic cell hybrid panel was constructed which includes hybrids containing the abnormal chromosome 17 from three MDS patients with deletions of various sizes. Three genes (myosin heavy chain 2, tumor antigen p53, and RNA polymerase II) previously mapped to 17p were excluded from the MDS deletion region and therefore are unlikely to play a role in its pathogenesis. In contrast, three highly polymorphic anonymous probes, YNZ22.1 (D17S5), YNH37.3 (D17S28), and 144-D6 (D17S34), were deleted in each of four patients with visible deletions, including one with a ring chromosome 17 that is deleted for a portion of the single telomeric prometaphase subband p13.3. In two MDS patients with normal chromosomes, a combination of somatic cell hybrid, RFLP, and densitometric studies demonstrated deletion for YNZ22.1 and YNH37.3 in the paternally derived 17's of both patients, one of whom is also deleted for 144-D6. The results indicate that MDS can be caused by submicroscopic deletion and raises the possibility that all MDS patients will prove to have deletions at a molecular level. The two probes lie within a critical region of less than 3,000 kb and constitute potential starting points in the isolation of genes implicated in the severe brain maldevelopment in MDS.