Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome
Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome
复制标题
DOI：
10.1086/375179
复制
发表时间：
2003-05-01
影响因子：
9.8
通讯作者：
Shaffer, LG
中科院分区：
文献类型：
--
作者：
Heilstedt, HA;Ballif, BC;Shaffer, LG
单体1 p36是最常见的末端缺失综合征。这种连续基因缺失综合征可能是由许多基因的单倍不足引起的。我们已经构建了重叠的大插入克隆的重叠群的最远端10.5 Mb的1 p36，评估了缺失的大小在61个主题与单体1 p36从60个家庭，并创建了一个自然的缺失面板。我们发现了纯末端缺失、间质缺失、衍生染色体和更复杂的重排。将断点“分箱”到0.5-Mb区域中。分析显示一些断点的聚类，但没有单一的共同断点。确定父母的起源表明，60%的从头1 p36末端缺失来自母系遗传的染色体。在61名受试者中，有30人通过德克萨斯儿童医院综合临床研究中心的一项协议进行了系统检查。具体来说，我们报告听力评估，腭和眼科检查，超声心动图，神经系统评估和甲状腺功能测试。据我们所知，这一系统的分子和临床表征的单体1 p36是最大和最全面的研究，这种缺失综合征的日期。正如我们的研究在分子水平上揭示的那样，许多细胞遗传学可见的、明显的末端缺失比细胞遗传学预期的更复杂。我们的临床研究结果允许更准确地识别综合征和适当的医疗评估。
Monosomy 1p36 is the most common terminal deletion syndrome. This contiguous gene deletion syndrome is presumably caused by haploinsufficiency of a number of genes. We have constructed a contig of overlapping large-insert clones for the most distal 10.5 Mb of 1p36, evaluated the deletion sizes in 61 subjects with monosomy 1p36 from 60 families, and created a natural deletion panel. We found pure terminal deletions, interstitial deletions, derivative chromosomes, and more complex rearrangements. Breakpoints were "binned" into 0.5-Mb regions. Analyses revealed some clustering of breakpoints but no single common breakpoint. Determination of the parental origin showed that 60% of de novo 1p36 terminal deletions arose from the maternally inherited chromosome. Of the 61 subjects, 30 were examined systematically through a protocol at the Texas Children's Hospital General Clinical Research Center. Specifically, we report hearing evaluations, palatal and ophthalmological examinations, echocardiograms, neurological assessments, and thyroid function tests. To our knowledge, this systematic molecular and clinical characterization of monosomy 1p36 is the largest and most comprehensive study of this deletion syndrome to date. Many cytogenetically visible, apparent terminal deletions are more complex than anticipated by cytogenetics, as revealed at the molecular level by our study. Our clinical findings allow for the more accurate recognition of the syndrome and for proper medical evaluation.