Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Am J Hum Genet. 2009 Dec;85(6):897-902. doi: 10.1016/j.ajhg.2009.10.027.
Although autosomal genes are increasingly recognized as important causes of intellectual disability, very few of them are known. We identified a genetic locus for autosomal-recessive nonsyndromic intellectual disability associated with variable postnatal microcephaly through homozygosity mapping of a consanguineous Israeli Arab family. Sequence analysis of genes in the candidate interval identified a nonsense nucleotide change in the gene that encodes TRAPPC9 (trafficking protein particle complex 9, also known as NIBP), which has been implicated in NF-kappaB activation and possibly in intracellular protein trafficking. TRAPPC9 is highly expressed in the postmitotic neurons of the cerebral cortex, and MRI analysis of affected patients shows defects in axonal connectivity. This suggests essential roles of TRAPPC9 in human brain development, possibly through its effect on NF-kappaB activation and protein trafficking in the postmitotic neurons of the cerebral cortex.
虽然常染色体基因越来越被认为是智力障碍的重要原因，但已知的非常少。我们通过对一个近亲以色列阿拉伯家庭的同系性作图，鉴定出一个与可变的产后小头畸形相关的常染色体隐性非综合征性智力障碍的遗传位点。在候选区间的基因的序列分析中，发现了一个编码 TRAPPC9（ trafficking protein particle complex 9，也称为 NIBP）的基因中的无义核苷酸变化，该基因已被牵连到 NF-kappaB 的激活，并可能参与细胞内蛋白质运输。TRAPPC9 在大脑皮质的有丝分裂后神经元中高度表达，受影响患者的 MRI 分析显示轴突连接缺陷。这表明 TRAPPC9 在人类大脑发育中具有重要作用，可能通过其对 NF-kappaB 激活和大脑皮质有丝分裂后神经元中蛋白质运输的影响。
