Normandie Univ, UNIROUEN, Inserm U1245, CHU Rouen, Department of Genetics and reference center for developmental disorders, FHU G4 Génomique, F-76000, Rouen, France.
Department of Medical Genetics and Embryology, Armand-Trousseau Children Hospital, AP-HP, Paris, France.
Am J Med Genet A. 2021 Oct;185(10):3057-3061. doi: 10.1002/ajmg.a.62361. Epub 2021 May 27.
Balanced translocations are associated with a risk of transmission of unbalanced chromosomal rearrangements in the offspring. Such inherited chromosomal abnormalities are typically non-mosaic as they are present in the germline. We report the recurrence in two siblings of a mosaicism for a chromosomal rearrangement inherited from their asymptomatic father who carried a balanced t(2;11)(q35;q25) translocation. Both siblings exhibited a similar phenotype including intellectual disability, dysmorphic features, kyphoscoliosis, and cervical spinal stenosis. Karyotyping, fluorescence in situ hybridization and SNP array analysis of blood lymphocytes of both siblings identified two cell lines: one carrying a 2q35q37.3 duplication and a 11q25qter deletion (90% cells), and one carrying an 11q uniparental isodisomy of maternal origin (10% cells). We hypothesize that these mosaics were related to a postzygotic rescue mechanism which unexpectedly recurred in both siblings.
平衡易位与后代不平衡染色体重排的传递风险相关。这种遗传性染色体异常通常是非嵌合性的，因为它们存在于生殖细胞中。我们报告了一对同卵双胞胎的嵌合体，其从无症状的父亲那里遗传了一条染色体重排，父亲携带平衡的 t(2;11)(q35;q25)易位。这对双胞胎都表现出相似的表型，包括智力障碍、畸形特征、脊柱后凸和颈椎椎管狭窄。对这对双胞胎的血液淋巴细胞进行核型分析、荧光原位杂交和 SNP 芯片分析，发现了两种细胞系：一种携带 2q35q37.3 重复和 11q25q 末端缺失（90%的细胞），另一种携带 11q 单亲二体性，来源于母系（10%的细胞）。我们假设这些嵌合体与合子后拯救机制有关，这种机制在这对双胞胎中意外地再次发生。
