Lundin Johanna, Söderhäll Cilla, Lundén Lina, Hammarsjö Anna, White Iréne, Schoumans Jacqueline, Läckgren Göran, Kockum Christina Clementson, Nordenskjöld Agneta
Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
Eur J Med Genet. 2010 Mar-Apr;53(2):61-5. doi: 10.1016/j.ejmg.2009.11.004. Epub 2010 Jan 4.
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.
膀胱外翻是膀胱和尿道的一种先天性畸形。这种畸形的遗传基础尚不清楚，然而众所周知，染色体畸变可导致器官发育缺陷。已有少数膀胱外翻患者被描述携带染色体畸变。22q11.2的染色体重排与几种基因组疾病有关，即迪格奥尔格综合征/心脏颜面综合征和猫眼综合征。该染色体区域内的缺失相对常见，而22q11.2的重复则较少见。越来越多关于该区域微重复的报告描述了高度可变的表型。我们对36名瑞典膀胱外翻患者进行了比较基因组杂交芯片分析。分析在两例患有膀胱外翻和听力障碍的无关病例中发现了一个相似的、约3 Mb的重复，这与最近描述的22q11.2微重复综合征一致。这一发现通过多重连接依赖探针扩增（MLPA）和荧光原位杂交（FISH）分析得到证实。随后对33名膀胱外翻患者该染色体区域进行的MLPA分析未发现该区域内有任何缺失/重复。对171名匿名对照个体进行的MLPA分析发现有一名个体携带这种微重复。这是与膀胱外翻和听力障碍相关的22q11.2微重复的首次报告。此外，在一组正常对照中发现一名携带者，这进一步凸显了与这种微重复综合征相关的可变表型。
