Interstitial Deletion of Proximal 8q Including Part of the Centromere from Unbalanced Segregation of a Paternal Deletion/Marker Karyotype with Neocentromere Formation at 8p22
Interstitial Deletion of Proximal 8q Including Part of the Centromere from Unbalanced Segregation of a Paternal Deletion/Marker Karyotype with Neocentromere Formation at 8p22
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DOI：
10.1159/000322815
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发表时间：
2011-01-01
影响因子：
1.7
通讯作者：
Warburton, P. E.
中科院分区：
文献类型：
--
作者：
Burnside, R. D.;Ibrahim, J.;Warburton, P. E.
背景/目的：染色体断裂和着丝粒错误分裂的McClintock机制，即形成缺失的染色体及其伴随的切除标记或环染色体，已有十几篇报道。我们报告一例身材矮小、发育迟缓和畸形的女孩。方法：采用细胞遗传学方法和Affymetrix6.0SNP微阵列对先证者和父亲进行分析。用8号染色体α-卫星探针进行荧光原位杂交(FISH)，并用CENP-C抗体进行免疫荧光检测着丝粒位置。结果：SNP阵列进一步将细胞遗传学可见缺失的异常8号染色体定义为8q11.1-gt；q12.1的10.6-Mb缺失。用8号染色体的α-卫星探针进行的FISH表明，该缺失去除了很大一部分着丝粒周围的α-卫星重复序列和近端的Q臂。缺失的8号染色体在8p22出现收缩，暗示形成了新的着丝粒，尽管阿尔法卫星序列仍然出现在正常位置。对表型正常的父亲进行染色体分析，发现了相同的缺失的8号染色体，以及一个明显平衡的镶嵌标记8号染色体。FISH研究表明，大部分8号染色体的α卫星DNA位于标记染色体上。对动粒蛋白CENP-C抗体的免疫荧光研究证明，在8p22处存在新着丝粒。从缺失的8号染色体上切除该标记可能需要在8p22新着丝粒上形成新的着丝粒，以在有丝分裂期间稳定染色体。结论：此病例清楚地说明了经典细胞遗传学、FISH和阵列技术的应用，以更好地描述染色体异常并提供有关复发风险的信息。这也代表了一种罕见的情况，即使在现有的阿尔法卫星DNA存在的情况下也能形成新的着丝粒。版权所有(C)2011 S.Karger AG，巴塞尔
Background/Aims: The 'McClintock mechanism' of chromosome breakage and centromere misdivision, in which a deleted chromosome with its concomitant excised marker or ring chromosome is formed, has been described in approximately one dozen reports. We report a case of a girl with short stature, developmental delay, and dysmorphic features. Methods: Analysis was performed on the proband and father using cytogenetic chromosome analysis and the Affymetrix 6.0 SNP microarray. Fluorescence in situ hybridization (FISH) using a chromosome 8 alpha-satellite probe and immunofluorescence with antibodies to CENP-C were used to examine the centromere positions in these chromosomes. Results: An abnormal chromosome 8 with a cytogenetically visible deletion was further defined by SNP array as a 10.6-Mb deletion from 8q11.1 -> q12.1. FISH with a chromosome 8 alpha-satellite probe demonstrated that the deletion removed a significant portion of the pericentromeric alpha-satellite repeat sequences and proximal q arm. The deleted chromosome 8 appeared to have a constriction at 8p22, suggesting the formation of a neocentromere, even though alpha-satellite sequences still appeared at the normal location. Chromosome analysis of the phenotypically normal father revealed the same deleted chromosome 8, as well as an apparently balancing mosaic marker chromosome 8. FISH studies revealed that the majority of the chromosome 8 alpha-satellite DNA resided in the marker chromosome. Immunofluorescence studies with antibodies to CENP-C, a kinetochore protein, proved the presence of a neocentromere at 8p22. The excision of the marker from the deleted chromosome 8 likely necessitated the formation of a new kinetochore at the 8p22 neocentromere to stabilize the chromosome during mitosis. Conclusion:This case clearly illustrates the utilization of classic cytogenetics, FISH, and array technologies to better characterize chromosomal abnormalities and provide information on recurrence risks. It also represents a rare case where a neocentromere can form even in the presence of existing alpha-satellite DNA. Copyright (C) 2011 S. Karger AG, Basel