Identification of a Recurrent Microdeletion at 17q23.1q23.2 Flanked by Segmental Duplications Associated with Heart Defects and Limb Abnormalities
Identification of a Recurrent Microdeletion at 17q23.1q23.2 Flanked by Segmental Duplications Associated with Heart Defects and Limb Abnormalities
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DOI：
10.1016/j.ajhg.2010.01.038
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发表时间：
2010-03-12
影响因子：
9.8
通讯作者：
Shaffer, Lisa G.
中科院分区：
文献类型：
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作者：
Ballif, Blake C.;Theisen, Aaron;Shaffer, Lisa G.
部分重复约占人类基因组的5%-10%，已知通过非等位基因同源重组介导医学相关的缺失、重复和倒置，并被认为是染色体进化和人类基因组不稳定的热点。我们报告了7个在17q23.1q23.2位点有微缺失的个体，通过基于微阵列的比较基因组杂交（aCGH）鉴定。7个缺失中有6个大小约为2.2 Mb，两侧存在相同方向、相同序列一致性达98%的大片段重复。其中一个缺失的大小约为2.8 Mb，在远端两侧有一个片段复制，而近端断点位于片段复制之间。这些特征表明，NAHR介导了7个重排中的6个。这些个体具有共同特征，包括轻度至中度发育迟缓（特别是言语迟缓）、小头畸形、出生后生长迟缓、心脏缺陷以及手、脚和肢体异常。尽管所有的个体都至少有轻微的面部畸形特征，但没有特征星座会引起临床对特定疾病的怀疑。共同临床特征的鉴定表明，17q23.1q23.2的微缺失构成了一种新的综合征。此外，在TBX2和TBX4的最小缺失区包含转录因子，这些转录因子属于涉及多种发育途径的基因家族，包括心脏和肢体的发育途径，这表明这些基因可能在这种新出现的综合征的表型中发挥重要作用。
Segmental duplications, which comprise similar to 5%-10% of the human genome, are known to mediate medically relevant deletions, duplications, and inversions through nonallelic homologous recombination (NAHR) and have been suggested to be hot spots in chromosome evolution and human genomic instability. We report seven individuals with microdeletions at 17q23.1q23.2, identified by microarray-based comparative genomic hybridization (aCGH). Six of the seven deletions are similar to 2.2 Mb in size and flanked by large segmental duplications of >98% sequence identity and in the same orientation. One of the deletions is similar to 2.8 Mb in size and is flanked on the distal side by a segmental duplication, whereas the proximal breakpoint falls between segmental duplications. These characteristics suggest that NAHR mediated six out of seven of these rearrangements. These individuals have common features, including mild to moderate developmental delay (particularly speech delay), microcephaly, postnatal growth retardation, heart defects, and hand, foot, and limb abnormalities. Although all individuals had at least mild dysmorphic facial features, there was no characteristic constellation of features that would elicit clinical Suspicion of a specific disorder. The identification of common clinical features suggests that microdeletions at 17q23.1q23.2 constitute a novel syndrome. Furthermore, the inclusion in the minimal deletion region of TBX2 and TBX4, transcription factors belonging to a family of genes implicated in a variety of developmental pathways including those of heart and limb, suggests that these genes may play an important role in the phenotype of this emerging syndrome.