Wong Keith, Moldrich Randal, Hunter Matthew, Edwards Matthew, Finlay David, O'Donnell Sheridan, MacDougall Tom, Bain Nicole, Kamien Benjamin
The University of Newcastle, School of Medicine and Public Health, Newcastle, New South Wales, Australia.
The University of Queensland, The UQ Centre for Clinical Research, Brisbane, Queensland, Australia.
Am J Med Genet A. 2015 Sep;167A(9):2201-8. doi: 10.1002/ajmg.a.37143. Epub 2015 May 5.
Small chromosomal duplications involving 7q36.3 have rarely been reported. This clinical report describes four individuals from a three-generation family with agenesis of the corpus callosum (ACC) and a 0.73 Mb duplication of 7q36.3 detected by array CGH. The 7q36.3 duplication involves two genes: RNA Binding Motif Protein 33 (RBM33) and Sonic Hedgehog (SHH). Most affected family members had mild intellectual disability or borderline intellectual functioning, macrocephaly, a broad forehead, and widely spaced eyes. Two individuals had a Chiari type I malformation. This is the first family reported with ACC associated with a small duplication of these genes. While we cannot establish causation for the relationship between any single gene and the ACC in this family, there is a role for SHH in the formation of the corpus callosum through correct patterning and assembly of the commissural plate, and these data concur with vertebrate studies showing that a gain of SHH expands the facial primordium.
涉及7q36.3的小染色体重复鲜有报道。本临床报告描述了一个三代家庭中的四名个体，他们患有胼胝体发育不全（ACC），并通过阵列比较基因组杂交检测到7q36.3有0.73 Mb的重复。7q36.3重复涉及两个基因：RNA结合基序蛋白33（RBM33）和音猬因子（SHH）。大多数受影响的家庭成员有轻度智力残疾或边缘智力功能、巨头畸形、额头宽阔和眼距过宽。两名个体患有I型Chiari畸形。这是首个报道的与这些基因小重复相关的ACC家庭。虽然我们无法确定该家庭中任何单个基因与ACC之间关系的因果性，但SHH通过连合板的正确模式形成和组装在胼胝体形成中发挥作用，并且这些数据与脊椎动物研究一致，即SHH的增加会扩大面部原基。
