A FISH approach to defining the extent and possible clinical significance of deletions at the WAGR locus
A FISH approach to defining the extent and possible clinical significance of deletions at the WAGR locus
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DOI：
10.1136/jmg.34.3.207
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发表时间：
1997-03-01
影响因子：
4
通讯作者：
vanHeyningen, V
中科院分区：
文献类型：
--
作者：
Crolla, JA;Cawdery, JE;vanHeyningen, V
19例患者进行了分析，荧光原位杂交（FISH）与选定的11 p13标记。他们被检查，因为他们有孤立的散发性或家族性无虹膜，或无虹膜与一个或多个WAGR（Wilms）肿瘤，无虹膜，生殖器异常，和精神发育迟滞）综合征异常。来自远端11 p13的FISH标记物是粘粒FO 2121、PAX 6（无虹膜）、D11 S324和WT 1（Wilms肿瘤易感性）。两名患者孤立无虹膜异常，一个明显的平衡相互7;11易位和11 p13断点，这是由FISH显示为类似于30 kb的远端无虹膜（PAX 6）基因，和其他有一个亚显微镜缺失涉及PAX 6的一部分，远端延伸到类似245 kb。2例无虹膜合并其他WAGR畸形的患者，其4个染色体均缺失。1例与发育和生长延迟相关的无虹膜病例的缺失包括FO 2121和PAX 6，但不包括D11 S324和WT 1，而在另1例病例中，缺失包括所有4种供试辅酶。这些研究表明，对无虹膜患者采用常规和分子细胞遗传学相结合的方法是一种有用的方法，可用于区分那些缺失延伸到WT 1并包括WT 1的患者，因此也可用于区分那些具有发展肾母细胞瘤的高风险和低风险的患者。
Nineteen patients were analysed by fluorescence in situ hybridisation (FISH) with selected 11p13 markers. They were examined because they had either isolated sporadic or familial aniridia, or aniridia with one or more of the WAGR (Wilms) tumour, aniridia, genital anomalies, and mental retardation) syndrome anomalies. The FISH markers from distal 11p13 were cosmids FO2121, PAX6 (aniridia), D11S324, and WT1 (Wilms) tumour predisposition). Two of the patients with isolated aniridia were abnormal, one with an apparently balanced reciprocal 7;11 translocation and an 11p13 breakpoint, which by FISH was shown to be similar to 30 kb distal to the aniridia (PAX6) gene, and the other had a submicroscopic deletion involving part of PAX6 that extended distally for similar to 245 kb. Two patients with aniridia together with other WAGR malformations had deletions involving all four cosmids. One case with aniridia associated with developmental and growth delay had a deletion including FO2121 and PAX6 but not D11S324 and WT1, while in a further case the deletion included all four test cosmids. These studies show that a combined conventional and molecular cytogenetic approach to patients presenting with aniridia is a useful method for differentiating between those with deletions extending into and including WT1 and therefore between those with high and low risks of developing Wilms' tumour.