MODIFICATION OF 15Q11-Q13 DNA METHYLATION IMPRINTS IN UNIQUE ANGELMAN AND PRADER-WILLI PATIENTS
MODIFICATION OF 15Q11-Q13 DNA METHYLATION IMPRINTS IN UNIQUE ANGELMAN AND PRADER-WILLI PATIENTS
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DOI：
10.1093/hmg/2.9.1377
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发表时间：
1993-09-01
影响因子：
3.5
通讯作者：
DRISCOLL, DJ
中科院分区：
文献类型：
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作者：
GLENN, CC;NICHOLLS, RD;DRISCOLL, DJ
人类基因组印记最明显的例子来自Angelman综合征（AS）和Prader - Willi综合征（PWS）的研究。尽管这两种疾病在临床上是不同的，但它们通常都是由于同一染色体区域15q11 - q13的缺失造成的。AS通常是由母亲的这一区域缺失或父亲的单亲二体（UPD，两条染色体都遗传自父亲）引起的。PWS是由父亲的15q11 - q13缺失或母亲的15号染色体UPD引起的。我们最近在15q11 - q13区域的D15S9位点（新基因符号，ZNF127）的基因上描述了一个亲本特异性DNA甲基化印记，该印记可以识别AS和PWS患者的缺失或UPD。在这里，我们描述了一个AS兄弟姐妹和三个PWS患者，其中15号染色体重排改变了ZNF127的甲基化状态，尽管这个位点并不直接参与重排。在没有可检测到的15号染色体缺失或UPD的AS兄弟姐妹中，父母特异性DNA甲基化印记在ZNF127和D15S63（另一个具有父母特异性甲基化印记的位点）也发生了改变。这些独特的患者可能为人类近端15号染色体的印迹过程提供见解。
The clearest example of genomic imprinting in humans comes from studies of the Angelman (AS) and Prader - Willi (PWS) syndromes. Although these are clinically distinct disorders, both typically result from a loss of the same chromosomal region, 15q11 - q13. AS usually results from either a maternal deletion of this region, or paternal uniparental disomy (UPD; both chromosomes 15 inherited from the father). PWS results from paternal deletion of 15q11 - q13 or maternal UPD of chromosome 15. We have recently described a parent-specific DNA methylation imprint in a gene at the D15S9 locus (new gene symbol, ZNF127), within the 15q11 - q13 region, that identifies AS and PWS patients with either a deletion or UPD. Here we describe an AS sibship and three PWS patients in which chromosome 15 rearrangements alter the methylation state at ZNF127, even though this locus is not directly involved in the rearrangement. Parent-specific DNA methylation imprints are also altered at ZNF127 and D15S63 (another locus with a parent-specific methylation imprint) in an AS sibship which have no detectable deletion or UPD of chromosome 15. These unique patients may provide insight into the imprinting process that occurs in proximal chromosome 15 in humans.