Vlaikou Angeliki-Maria, Manolakos Emmanouil, Noutsopoulos Dimitrios, Markopoulos Georgios, Liehr Thomas, Vetro Annalisa, Ziegler Monika, Weise Anja, Kreskowski Katharina, Papoulidis Ioannis, Thomaidis Loretta, Syrrou Maria
Laboratory of General Biology, Medical School, University Campus, Ioannina, Greece.
Cytogenet Genome Res. 2014;142(4):227-38. doi: 10.1159/000361001. Epub 2014 Apr 9.
The 4q deletion syndrome phenotype consists of growth failure and developmental delay, minor craniofacial dysmorphism, digital anomalies, and cardiac and skeletal defects. We have identified an inversion (inv(1)(q25.2q31.1)) and an interstitial deletion in a boy with developmental delay using array-comparative genomic hybridization. This de novo deletion is located at 4q31.21q31.22 (145,963,820- 147,044,764), its size is 0.9-1.1 Mb, and it contains 7 genes (ABCE1, OTUD4, SMAD1, MMAA, C4orf51, ZNF827, and ANAPC10) as well as 5 retrotransposon-derived pseudogenes. Bioinformatic analysis revealed that while small copy number variations seem to have no impact on the phenotype, larger deletions or duplications in the deleted region are associated with developmental delay. Additionally, we found a higher coverage in transposable element sequences in the 4q31.21q31.22 region compared to that of the expected repeat density when regarding any random genome region. Transposable elements might have contributed to the reshaping of the genome architecture and, most importantly, we identified 3 L1PA family members in the breakpoint regions, suggesting their possible contribution in the mechanism underlying the appearance of this deletion. In conclusion, this is one of the smallest deletions reported associated with developmental delay, and we discuss the possible role of genomic features having an impact on the phenotype.
4q缺失综合征的表型包括生长发育迟缓、轻微颅面畸形、手指异常以及心脏和骨骼缺陷。我们利用阵列比较基因组杂交技术，在一名发育迟缓的男孩中鉴定出一个倒位（inv(1)(q25.2q31.1)）和一个间质性缺失。这个新发缺失位于4q31.21q31.22（145,963,820 - 147,044,764），大小为0.9 - 1.1 Mb，包含7个基因（ABCE1、OTUD4、SMAD1、MMAA、C4orf51、ZNF827和ANAPC10）以及5个逆转座子衍生的假基因。生物信息学分析表明，虽然小的拷贝数变异似乎对表型没有影响，但缺失区域中较大的缺失或重复与发育迟缓相关。此外，我们发现与任何随机基因组区域的预期重复密度相比，4q31.21q31.22区域的转座元件序列覆盖度更高。转座元件可能对基因组结构的重塑有贡献，最重要的是，我们在断点区域鉴定出3个L1PA家族成员，提示它们可能在该缺失出现的潜在机制中发挥作用。总之，这是报道的与发育迟缓相关的最小缺失之一，我们讨论了对表型有影响的基因组特征的可能作用。
