The de novo chromosome 16 translocations of two patients with abnormal phenotypes (mental retardation and epilepsy) disrupt the A2BP1 gene
The de novo chromosome 16 translocations of two patients with abnormal phenotypes (mental retardation and epilepsy) disrupt the A2BP1 gene
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DOI：
10.1007/s10038-004-0145-4
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发表时间：
2004-06-01
影响因子：
3.5
通讯作者：
Callen, DF
中科院分区：
文献类型：
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作者：
Bhalla, K;Phillips, HA;Callen, DF
对16号染色体的两种新生易位t(1;16)和t(14;16)的16p13.3断点进行的初步定位研究表明，它们在物理上具有相邻的断点。这两种易位是在具有异常表型的患者中确定的，其中一名患者以癫痫为主，另一名患者有智力障碍。地丝菌素/DAPI显带显示t(1;16)的1号染色体断点位于着丝粒周围异染色质中，因此潜在的基因破坏局限于16p13.3断点。这两种易位的断点分别定位在3.5kb和115kb的区域，相距约900kb。通过对跨越断点的克隆与来自患者的中期分裂相进行荧光原位杂交（FISH），证实了定位结果。定位数据显示这两种易位都破坏了包含1.7Mb大基因组区域的ataxin - 2结合蛋白1（A2BP1）基因。A2BP1编码一种已知与脊髓小脑性共济失调2型（SCA2）蛋白相互作用的蛋白质。据推测，A2BP1基因的破坏是这两名患者异常表型的原因。通过单链构象多态性（SSCP）对96名散发性癫痫患者和96名女性智力障碍患者进行了A2BP1潜在突变的筛查。未发现突变，这表明A2BP1基因的破坏不是散发性癫痫或智力障碍的常见原因。
The 16p13.3 breakpoints of two de novo translocations of chromosome 16, t(1;16) and t(14;16), were shown by initial mapping studies to have physically adjacent breakpoints. The translocations were ascertained in patients with abnormal phenotypes characterized by predominant epilepsy in one patient and mental retardation in the other. Distamycin/DAPI banding showed that the chromosome 1 breakpoint of the t(1;16) was in the pericentric heterochromatin therefore restricting potential gene disruption to the 16p13.3 breakpoint. The breakpoints of the two translocations were localized to a region of 3.5 and 115 kb respectively and were approximately 900 kb apart. The mapping was confirmed by fluorescence in situ hybridization (FISH) of clones that spanned the breakpoints to metaphase spreads derived from the patients. The mapping data showed both translocations disrupted the ataxin-2-binding protein 1 (A2BP1) gene that encompasses a large genomic region of 1.7 Mb. A2BP1 encodes a protein that is known to interact with the spinocerebellar ataxia type 2 (SCA2) protein. It is proposed that disruption of the A2BP1 gene is a cause of the abnormal phenotype of the two patients. Ninety-six patients with sporadic epilepsy and 96 female patients with mental retardation were screened by SSCP for potential mutations of A2BP1. No mutations were found, suggesting that disruption of the A2BP1 gene is not a common cause of sporadic epilepsy or mental retardation.