Stevenson R E
Greenwood Genetic Center, 1 Gregor Mendel Circle, Greenwood, SC 29646, USA.
Am J Med Genet. 2000 Fall;97(3):174-82. doi: 10.1002/1096-8628(200023)97:3<174::AID-AJMG1034>3.0.CO;2-4.
Although it is assumed that genes that influence cognitive function are ubiquitous in the human genome, to date, more such genes have been found on the X chromosome than on any other comparable segment of the autosomes. This is in large measure because of the power of hemizygosity in exposing mutations of X-linked genes in males. Clinical manifestations, mapping of gene loci by linkage analysis or chromosome rearrangements, and gene identification by positional cloning or mutational analysis of candidate genes have permitted extensive lumping and splitting within the large and heterogeneous category of X-linked mental retardation (XLMR). Approximately 130 XLMR syndromes have been identified, 25 gene loci have been mapped and cloned, and 55 other loci have been mapped but not cloned. Well-recognized syndromes (e.g., Fragile X and Coffin-Lowry syndromes) and syndromes represented by only a single family (e.g., Arena and monoamine oxidase-A syndromes) are among these more or less well-defined entities. In addition, more than 75 families with nonsyndromal XLMR have been regionally mapped and 7 causative genes have been identified.
尽管人们认为影响认知功能的基因在人类基因组中普遍存在，但迄今为止，在X染色体上发现的这类基因比常染色体上任何其他可比片段都要多。这在很大程度上是因为半合子状态在暴露男性X连锁基因的突变方面具有强大作用。通过连锁分析或染色体重排对基因座进行定位，以及通过定位克隆或候选基因突变分析进行基因鉴定，使得在X连锁智力障碍（XLMR）这个庞大且异质性的类别中进行了广泛的归类和细分。大约已经确定了130种XLMR综合征，25个基因座已被定位和克隆，另外55个基因座已被定位但尚未克隆。这些或多或少已明确的实体中包括广为人知的综合征（如脆性X综合征和科芬-洛里综合征）以及仅由一个家族代表的综合征（如阿雷纳综合征和单胺氧化酶A综合征）。此外，已经对75多个非综合征性XLMR家族进行了区域定位，并确定了7个致病基因。
