22q11.2 microduplication in two patients with bladder exstrophy and hearing impairment
22q11.2 microduplication in two patients with bladder exstrophy and hearing impairment
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DOI：
10.1016/j.ejmg.2009.11.004
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发表时间：
2010-03-01
影响因子：
1.9
通讯作者：
Nordenskjold, Agneta
中科院分区：
文献类型：
--
作者：
Lundin, Johanna;Soderhall, Cilla;Nordenskjold, Agneta
膀胱外翻是一种先天性膀胱和尿道畸形。这种畸形的遗传基础尚不清楚，但众所周知，染色体畸变可导致器官发育缺陷。少数膀胱外翻患者已被描述为携带染色体畸变。22q11.2的染色体重排涉及几种基因组疾病，即DiGeorge/velocardiofacial- and cat-eye综合征。该染色体区域内的缺失相对常见，而22q11.2的重复则不太常见。越来越多的报告微重复这一地区描述了一个高度可变的phenotype.We进行了阵列CGH分析36瑞典膀胱外翻患者。分析显示，在两个不相关的膀胱外翻和听力障碍的情况下，类似的，约3 Mb的重复，与最近描述的22q11.2微重复综合征一致。这一发现证实了多重连接依赖性探针扩增（MLPA）和FISH分析。随后MLPA分析33例膀胱外翻患者的该染色体区域未发现该区域内有任何缺失/重复。MLPA分析171名匿名对照者，发现1人携带这种微重复，这是首次报道的22q11.2微重复与膀胱外翻和听力障碍相关。此外，在正常对照组中发现一名携带者进一步强调了与这种微复制综合征相关的可变表型。(C)2010年Elsevier Masson SAS。All rights reserved.
Bladder exstrophy is a congenital malformation of the bladder and urethra. The genetic basis of this malformation is unknown however it is well known that chromosomal aberrations can lead to defects in organ development. A few bladder exstrophy patients have been described to carry chromosomal aberrations. Chromosomal rearrangements of 22q11.2 are implicated in several genomic disorders i.e. DiGeorge/velocardiofacial- and cat-eye syndrome. Deletions within this chromosomal region are relatively common while duplications of 22q11.2 are much less frequently observed. An increasing number of reports of microduplications of this region describe a highly variable phenotype.We have performed array-CGH analysis of 36 Swedish bladder exstrophy patients. The analysis revealed a similar and approximately 3 Mb duplication, consistent with the recently described 22q11.2 microduplication syndrome, in two unrelated cases with bladder exstrophy and hearing impairment. This finding was confirmed by multiplex ligation-dependent probe amplification (MLPA) and FISH analysis. Subsequent MLPA analysis of this chromosomal region in 33 bladder exstrophy patients did not reveal any deletion/duplication within this region. MLPA analysis of 171 anonymous control individuals revealed one individual carrying this microduplication.This is the first report of 22q11.2 microduplication associated with bladder exstrophy and hearing impairment. Furthermore the finding of one carrier among a cohort of normal controls further highlights the variable phenotype linked to this microduplication syndrome. (C) 2010 Elsevier Masson SAS. All rights reserved.