Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Am J Med Genet A. 2011 Jan;155A(1):9-13. doi: 10.1002/ajmg.a.33663. Epub 2010 Dec 10.
Involvement of genes on the X-chromosome as a cause of mental retardation has been recognized for a long time. X-linked phenotypes of mental retardation have been divided into non-syndromic and syndromic based on associated manifestations. At present, more than 140 syndromic X-linked mental retardation (XLMR) conditions have been reported and a causative gene mutation has been identified in almost half of these. Here, we report on two brothers with short stature, microcephaly, severe mental retardation, and retinoschisis. Results of karyotype analysis, fragile-X and neuroimaging studies were normal. Fundus examination showed bilateral retinoschisis at variable stages in both sibs. X-linked retinoschisis is a retinal dystrophy caused by mutations in the RS1 gene at Xp22.1, which lead to splitting of the neural retina and reduced visual acuity in affected men. However, as yet there have been no reports of mental retardation in X-linked retinoschisis although genetic loci for XLMR and short stature have been mapped to Xp22.1. Sequencing and microarray analysis failed to find any alteration of RS1 gene or copy number alteration in the region. In addition, genotype analysis of Xp22.1 provided evidence against linkage to this region. The associated findings of retinoschisis and mental retardation in two brothers suggest a new mental retardation syndrome likely to be an X linked trait.
X 染色体基因异常导致精神发育迟滞早已得到公认。根据伴发症状，X 连锁智力低下表型可分为非综合征型和综合征型。目前已报道超过 140 种 X 连锁智力低下（XLMR）综合征，其中近半数的综合征型已确定致病基因突变。本研究报道了两例兄弟，他们身材矮小、头小畸形、智力严重低下，并有视网膜劈裂。核型分析、脆性 X 综合征和神经影像学研究结果均正常。眼底检查显示两兄弟双侧视网膜劈裂，处于不同阶段。X 连锁视网膜劈裂症是由 Xp22.1 上 RS1 基因突变引起的视网膜营养不良，导致神经视网膜分裂和受累男性视力下降。然而，尽管已定位到 XLMR 和身材矮小的遗传位点，但 X 连锁视网膜劈裂症尚未有智力低下的报道。对 RS1 基因进行测序和微阵列分析，均未发现该区域有任何基因改变或拷贝数改变。此外，Xp22.1 的基因型分析也排除了与该区域的连锁。两兄弟的视网膜劈裂伴智力低下的相关发现提示可能存在一种新的智力低下综合征，且为 X 连锁遗传特征。
