Detection of deletions and cryptic translocations in Miller-Dieker syndrome by in situ hybridization.
Detection of deletions and cryptic translocations in Miller-Dieker syndrome by in situ hybridization.
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发表时间：
1991-10
影响因子：
9.8
通讯作者：
A. Kuwano;S. Ledbetter;W. B. Dobyns;Beverly S. Emanuel;D. Ledbetter
中科院分区：
文献类型：
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作者：
A. Kuwano;S. Ledbetter;W. B. Dobyns;Beverly S. Emanuel;D. Ledbetter
采用荧光原位杂交(FISH)技术，对3例亚镜下缺失的MDS患者和4例正常对照家系进行了荧光原位杂交(FISH)。对照组显示，两个17号染色体的同源物都标记在85%-95%的细胞中，而每个患者只有一个同源物标记在75%-80%的细胞中。两名患有隐匿性易位的MDS患者也被研究。在一个病例中，患者和她的母亲有相同的DER(17)(p+)，但通过G显带无法在母亲身上识别出易位的互易产物(即，这是一种“半隐蔽”易位)。FISH发现了一个3Q；17P易位。另一例患者的核型明显正常。因为发现了一个大分子缺失，所以推测是涉及两个G-阴性端粒的易位(即“全隐蔽”易位)。对她父亲和正常兄弟的FISH研究显示，她有8q；17p易位。这些研究表明，原位杂交是检测Miller-Dieker综合征缺失的有效方法。更重要的是，FISH对表现出分子缺失和正常核型的患者进行的亲代研究可能会识别出隐蔽的易位事件，这是其他分子遗传策略无法检测到的。对于其他微缺失综合征，例如Prader-Willi/Angelman综合征或DiGeorge综合征，可以开发类似的原位缺失检测策略。
Fluorescence in situ hybridization (FISH) using two cosmid probes (41A and P13) from the Miller-Dieker syndrome (MDS) critical region in 17p13.3 was performed in a blinded comparison of three MDS patients with submicroscopic deletions and in four normal relatives used as controls. The controls showed both chromosome 17 homologues labeled in 85%-95% of cells, while each patient showed only one homologue labeled in 75%-80% of cells. Two MDS patients with cryptic translocations were also studied. In one case, a patient and her mother had the same der(17) (p+), but the reciprocal product of the translocation could not be identified in the mother by G-banding (i.e., it was a "half-cryptic" translocation). FISH revealed a 3q;17p translocation. The other case involved a patient with apparently normal karyotype. Because a large molecular deletion was found, a translocation involving two G-negative telomeres (i.e., a "full-cryptic" translocation) was postulated. FISH studies on her father and normal brother showed an 8q;17p translocation. These studies demonstrate that in situ hybridization is an efficient method for deletion detection in Miller-Dieker syndrome. More important, parental studies by FISH on patients demonstrating molecular deletions and a normal karyotype may identify cryptic translocation events, which cannot be detected by other molecular genetic strategies. Similar in situ strategies for deletion detection can be developed for other microdeletion syndromes, such as Prader-Willi/Angelman syndrome or DiGeorge syndrome.