Genes and Disease Program, CIBER en Epidemiología y Salud Pública (CIBERESP), Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain.
BMC Med Genet. 2009 Dec 23;10:144. doi: 10.1186/1471-2350-10-144.
Microdeletion of the chromosome 22q11.2 region is the most common genetic aberration among patients with velocardiofacial syndrome (VCFS) but a subset of subjects do not show alterations of this chromosome region.
We analyzed 18 patients with VCFS-like features by comparative genomic hybridisation (aCGH) array and performed a face-to-face slide hybridization with two different arrays: a whole genome and a chromosome 22-specific BAC array. Putative rearrangements were confirmed by FISH and MLPA assays.
One patient carried a combination of rearrangements on 1q21.1, consisting in a microduplication of 212 kb and a close microdeletion of 1.15 Mb, previously reported in patients with variable phenotypes, including mental retardation, congenital heart defects (CHD) and schizophrenia. While 326 control samples were negative for both 1q21.1 rearrangements, one of 73 patients carried the same 212-kb microduplication, reciprocal to TAR microdeletion syndrome. Also, we detected four copy number variants (CNVs) inherited from one parent (a 744-kb duplication on 10q11.22; a 160 kb duplication and deletion on 22q11.21 in two cases; and a gain of 140 kb on 22q13.2), not present in control subjects, raising the potential role of these CNVs in the VCFS-like phenotype.
Our results confirmed aCGH as a successful strategy in order to characterize additional submicroscopic aberrations in patients with VCF-like features that fail to show alterations in 22q11.2 region. We report a 212-kb microduplication on 1q21.1, detected in two patients, which may contribute to CHD.
22q11.2 染色体微缺失是血管迷走性晕厥综合征（VCFS）患者中最常见的遗传异常，但一部分患者并未显示该染色体区域的改变。
我们通过比较基因组杂交（aCGH）阵列分析了 18 例具有 VCFS 样特征的患者，并使用两种不同的阵列（全基因组和 22 号染色体特异性 BAC 阵列）进行了面对面的滑动杂交。通过荧光原位杂交（FISH）和多重连接探针扩增（MLPA）检测推定的重排。
一位患者携带 1q21.1 上的重排组合，包括 212kb 的微重复和 1.15Mb 的微缺失，这在具有可变表型的患者中已有报道，包括智力障碍、先天性心脏缺陷（CHD）和精神分裂症。虽然 326 个对照样本均未出现 1q21.1 重排，但 73 例患者中有 1 例携带相同的 212kb 微重复，与 TAR 微缺失综合征相反。此外，我们还检测到来自一位父母的四个拷贝数变异（CNVs）（10q11.22 上的 744kb 重复；22q11.21 上的 160kb 重复和缺失，在两个病例中；以及 22q13.2 上的 140kb 增益），这些 CNVs 在对照样本中不存在，提示这些 CNVs 可能在 VCFS 样表型中发挥作用。
我们的结果证实了 aCGH 是一种成功的策略，可以用于描述具有 VCFS 样特征但未能显示 22q11.2 区域改变的患者的其他亚微观异常。我们报道了在两名患者中检测到的 1q21.1 上的 212kb 微重复，可能导致 CHD。
