Cho Ginam, Bhat Shambhu S, Gao Jinsong, Collins Julianne S, Rogers R Curtis, Simensen Richard J, Schwartz Charles E, Golden Jeffrey A, Srivastava Anand K
Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Am J Med Genet A. 2008 Oct 15;146A(20):2644-50. doi: 10.1002/ajmg.a.32472.
An estimated 1-3% of individuals within the United States are diagnosed with mental retardation (MR), yet the cause is unknown in nearly 50% of the patients. While several environmental, genetic and combined teratogenetic etiologies have been identified, many causative genes remain to be identified. Furthermore, the pathogenetic mechanisms underlying MR are known for very few of these genes. Males have a much higher incidence of MR implicating genes on the X-chromosome. We have recently identified a novel gene, SIZN1, on the X-chromosome and showed that it functions in modulating the BMP signaling pathway. Furthermore, we have shown this gene is necessary for basal forebrain cholinergic neuron (BFCN) specific gene expression. Given that cognitive function is impaired when BFCNs are lost or functionally disrupted, we undertook a screen of cognitively impaired males for SIZN1 mutations. We report on four different sequence variants in SIZN1 in 11 individuals with nonsyndromic X-linked mental retardation (XLMR). Our data implicate SIZN1 as a candidate gene for XLMR and/or as a neurocognitive functional modifier.
据估计，美国有1%至3%的人被诊断患有智力迟钝（MR），然而近50%的患者病因不明。虽然已经确定了几种环境、遗传和联合致畸病因，但许多致病基因仍有待确定。此外，这些基因中只有极少数的MR致病机制是已知的。男性MR发病率高得多，这表明X染色体上的基因有问题。我们最近在X染色体上发现了一个新基因SIZN1，并表明它在调节骨形态发生蛋白（BMP）信号通路中发挥作用。此外，我们还表明该基因是基底前脑胆碱能神经元（BFCN）特异性基因表达所必需的。鉴于当BFCN丢失或功能受损时认知功能会受到损害，我们对认知受损男性进行了SIZN1突变筛查。我们报告了11例非综合征性X连锁智力迟钝（XLMR）患者中SIZN1的四种不同序列变异。我们的数据表明SIZN1是XLMR的候选基因和/或神经认知功能修饰基因。
