Psychiatric disorder and cognitive function in a family with an inherited novel mutation of the developmental control gene PAX6
Psychiatric disorder and cognitive function in a family with an inherited novel mutation of the developmental control gene PAX6
复制标题
DOI：
10.1097/00041444-199906000-00006
复制
发表时间：
1999-06-01
影响因子：
0.9
通讯作者：
Simonoff, E
中科院分区：
文献类型：
--
作者：
Heyman, I;Frampton, I;Simonoff, E
已知PAX家族的发育控制基因在中枢神经系统的早期模式中发挥重要作用。这个家族的一个成员PAX6参与了无脊椎动物、小鼠和人类的眼睛发育，但也在发育中的前脑中广泛表达。携带该基因突变的人会出现眼睛发育异常，这里提出的结果首次表明，该突变也可能与所研究家庭中额叶功能的细微异常有关。我们对单个家族内的个体进行了基因分型，无论是否存在PAX6突变的特征性眼部异常，只有那些具有该突变的个体在额叶功能测试中表现出显著异常。这些人患精神疾病的几率也更高。PAX6在小鼠和人之间高度保守，尽管与PAX6杂合性相关的神经解剖学表型仅在小鼠中研究过，但在小鼠中看到的由此产生的细胞紊乱可能存在于人类前脑中。虽然这些小鼠没有明显的行为表型，但这里提出的结果表明，具有相同突变的人类表现出神经行为表型。(C) 1999 Lippincott Williams & Wilkins。
The PAX family of developmental control genes are known to play important roles in the early patterning of the central nervous system. One member of this family, PAX6, is involved in eye development in invertebrates as well as in mouse and man, but is also widely expressed in the developing forebrain. Humans with a mutation in this gene have abnormalities of eye development, and the results presented here suggest, for the first time, that this mutation may also be associated with subtle abnormalities of frontal lobe function in the family studied. We carried out genotyping of individuals within a single family, with and without the characteristic eye abnormalities of PAX6 mutation, and only those individuals with the mutation showed significant abnormalities on tests of frontal lobe function. These individuals also had higher rates of psychiatric disorder. PAX6 is highly conserved between mouse and man, and although the neuroanatomical phenotype associated with PAX6 heterozygosity has only been studied in mice, the resultant cellular disorganization seen in mice is likely to be present in the human forebrain. Although these mice have no obvious behavioural phenotype, the results presented here suggest that humans with the equivalent mutation display a neurobehavioural phenotype. (C) 1999 Lippincott Williams & Wilkins.