Piovani Giovanna, Borsani Giuseppe, Bertini Valeria, Kalscheuer Vera M, Viertel Petra, Bellotti Daniela, Valseriati Daniela, Barlati Sergio
Biology and Genetics Division, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Eur J Med Genet. 2006 May-Jun;49(3):215-23. doi: 10.1016/j.ejmg.2005.07.004. Epub 2005 Aug 25.
Interstitial deletions and pericentric inversions of chromosome 4 appear to be unusual phenomena. Here, we report the case of a 14-year-old boy with severe psychomotor retardation with a de novo 46,XY,der(4)del(p15.2p15.31)inv(4)(p15.2q13.3)del(4)(q13.2q13.2) karyotype. We used FISH analysis with YAC and BAC clones to characterise the inversion's breakpoints. A complex event with six breakpoints was found, characterised by a pericentric inversion and two deletions, the first on the short arm of chromosome 4 (4p) and the second on the long arm of chromosome 4 (4q). The deletion events had removed two segments, one of approximately 5 Mb, from 4p, outside the inversion, and the other 2 Mb from 4q, inside the inversion. These rearrangements were not found in the parents. Microsatellite marker analysis showed that the inversion carrying chromosome 4 was derived from the father. Bioinformatic analysis of the human genome sequence allowed us to identify several hemizygotic genes in the patient, which might be involved in the pathogenesis of this clinical phenotype.
4号染色体的间质性缺失和臂间倒位似乎是不寻常的现象。在此，我们报告一例14岁男孩，患有严重精神运动发育迟缓，其核型为46,XY,der(4)del(p15.2p15.31)inv(4)(p15.2q13.3)del(4)(q13.2q13.2)，系新发突变。我们使用YAC和BAC克隆进行荧光原位杂交（FISH）分析，以确定倒位的断点。发现了一个具有六个断点的复杂事件，其特征为一个臂间倒位和两个缺失，第一个缺失位于4号染色体短臂（4p），第二个缺失位于4号染色体长臂（4q）。缺失事件去除了两个片段，一个约5 Mb，位于倒位之外的4p上，另一个2 Mb，位于倒位之内的4q上。这些重排在其父母中未发现。微卫星标记分析表明，携带倒位的4号染色体来自父亲。对人类基因组序列的生物信息学分析使我们能够在患者中鉴定出几个半合子基因，这些基因可能与这种临床表型的发病机制有关。
