Wyandt Herman E, Shim Sung Han, Mark Hon Fong L, Huang Xin Li, Milunsky Jeff M
Center for Human Genetics, Boston University School of Medicine, Boston, MA 02118, USA.
Exp Mol Pathol. 2006 Jun;80(3):262-6. doi: 10.1016/j.yexmp.2005.12.008. Epub 2006 Mar 6.
A 10-year-old African-American male has been followed since 2 years of age due to his mental retardation, severe behavioral problems, and dysmorphism. Conventional cytogenetic analysis, chromosome painting, high-resolution comparative genomic hybridization (HR-CGH), and bacterial artificial chromosome fluorescent in situ hybridization (BAC FISH) revealed an apparent duplication in the short arm of a chromosome 11, dup(11)(p14.3p15.1), seen also in his mentally retarded mother. The proband had moderate to severe mental retardation, a history of IUGR, infantile hypotonia, FTT, exotropia, inguinal hernia repair, and several dysmorphic features. His mother had mild mental retardation, a history of impulsivity, assaultive outbursts, and similar dysmorphism. Although G-banding and FISH indicated a duplication, HR-CGH confined the localization of material to bands 11p14-11p15 and aided the selection of locus-specific BAC clones to more precisely characterize the duplicated region. To our knowledge, the results represent the first example of a familial, cytogenetically visible duplication of euchromatin in 11p that excludes the Beckwith-Wiedemann syndrome critical region. It is possible that one or more genes had been disrupted at the breakpoints of the above structural chromosomal rearrangement giving rise to the present phenotype.
一名10岁非裔美国男性自2岁起就因其智力发育迟缓、严重行为问题和畸形而接受跟踪观察。传统细胞遗传学分析、染色体涂染、高分辨率比较基因组杂交(HR-CGH)以及细菌人工染色体荧光原位杂交(BAC FISH)显示11号染色体短臂存在明显重复,即dup(11)(p14.3p15.1),在其智力发育迟缓的母亲身上也有发现。先证者有中度至重度智力发育迟缓、宫内生长受限史、婴儿期肌张力低下、生长发育迟缓、外斜视、腹股沟疝修补术以及一些畸形特征。他的母亲有轻度智力发育迟缓、冲动史、攻击性发作以及类似的畸形。尽管G显带和FISH表明存在重复,但HR-CGH将物质定位局限于11p14 - 11p15带,并有助于选择位点特异性BAC克隆以更精确地表征重复区域。据我们所知,这些结果代表了11p常染色质家族性细胞遗传学可见重复的首个例子,该重复排除了贝克威思-维德曼综合征关键区域。有可能一个或多个基因在上述染色体结构重排的断点处被破坏,从而导致了目前的表型。