Laboratoire d'Histologie, Cytologie et Cytogénétique, Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale, Brest, France.
Am J Med Genet A. 2011 Sep;155A(9):2281-7. doi: 10.1002/ajmg.a.34162. Epub 2011 Aug 10.
We report here three children with a der(11)t(11;16), two sibs (patients 1 and 2) having inherited a recombinant chromosome from a maternal t(11;16)(q24.3;q23.2) and a third unrelated child with a de novo der(11)t(11;16)(q25;q22.1), leading to partial monosomy 11q and trisomy 16q. Fluorescent in situ hybridization (FISH) using bacterial artificial chromosome (BAC) clones and array-CGH were performed to determine the breakpoints involved in the familial and the de novo rearrangements. The partial 11 monosomy extended from 11q24.3 to 11qter and measured 6.17-6.21 Mb in Patients 1 and 2 while the size of the partial 11q25->qter monosomy was estimated at 1.97-2.11 Mb for Patient 3. The partial 16 trisomy extended from 16q23.2 to 16qter and measured 8.93-8.95 Mb in Patients 1 and 2 while the size of the partial 16q22.1->qter trisomy was 20.82 Mb for Patient 3. Intraventricular hemorrhage and transitional thrombocytopenia were found in both sibs but not in the third patient. The FLI1 gene, which is the most relevant gene for thrombocytopenia in Jacobsen syndrome, was neither deleted in family A nor in Patient 3. We suggest that a positional effect could affect the FLI1 expression for these two sibs. Deafness of our three patients confirmed the association of this anomaly to 11q monosomy and tended to confirm the hypothetic role of DFNB20 in Jacobsen syndrome hearing loss. Both sibs shared most of the features commonly observed in Jacobsen syndrome, but not the third patient. This confirmed that terminal 11q trisomy spanning 1 to 1.97-2.11 Mb is not associated with a typical Jacobsen syndrome.
我们在此报告三例具有 der(11)t(11;16) 的患儿，其中两名同胞（患者 1 和 2）从母亲的 t(11;16)(q24.3;q23.2) 中遗传了重组染色体，而第三个无关的患儿则发生了从头的 der(11)t(11;16)(q25;q22.1)，导致 11q 部分单体和 16q 三体。使用细菌人工染色体 (BAC) 克隆和 array-CGH 进行荧光原位杂交 (FISH)，以确定家族性和从头重排涉及的断点。部分 11 单体从 11q24.3 延伸到 11qter，在患者 1 和 2 中测量为 6.17-6.21 Mb，而患者 3 中部分 11q25->qter 单体的大小估计为 1.97-2.11 Mb。部分 16 三体从 16q23.2 延伸到 16qter，在患者 1 和 2 中测量为 8.93-8.95 Mb，而患者 3 中部分 16q22.1->qter 三体的大小为 20.82 Mb。两名同胞均存在脑室出血和过渡性血小板减少症，但第三例患者没有。在 Jacobsen 综合征中与血小板减少症最相关的 FLI1 基因，在家族 A 中既没有缺失，也没有在患者 3 中缺失。我们认为，位置效应可能会影响这两个同胞的 FLI1 表达。我们三个患者的耳聋证实了这种异常与 11q 单体的关联，并倾向于证实 DFNB20 在 Jacobsen 综合征听力损失中的假设作用。两名同胞均具有 Jacobsen 综合征中常见的大多数特征，但第三例患者没有。这证实了跨越 1 至 1.97-2.11 Mb 的末端 11q 三体并不与典型的 Jacobsen 综合征相关。
