最近一项新的研究发现，男性精神疾病的严重程度不同与GDI1基因的拷贝数有关，该基因位于X-染色体上，GDI1基因的拷贝数越多，疾病也越严重。这项研究发表在最近一期的American Journal of Human Genetics杂志上。
科学家研究了患有相关疾病的好几个家族，通过研究首次发现精神病的严重程度与X染色体上GDI1基因的拷贝数有关。携带5个拷贝的GDI1基因一般比携带2个拷贝GDI1基因的智力低下程度更严重。
之前有研究人员发现一些X连锁的智力低下患者GDI1基因缺失。这些患者大脑内GDI1产生的途径被中断，导致各种刺激无法传递到大脑皮层。这项新的研究表明，过量产生GDI1对人的智力也同样有危害。
弱智在总人口中的发病比例为2--3%。造成这一缺陷有外部因素，如分娩时胎儿缺氧等；也有可能由于遗传因素决定。因此，准确找出导致缺陷的原因将有助于为患者提供更好的治疗方法。（生物谷Bioon.com）
人类智力研究：
BMC Neuroscience：用磁脉冲刺激大脑有助提高智力
PNAS：婴儿智商高低与母乳喂养无关 某种酶成关键因素
Am J Hum Genet.：MECP2的表达与男性的智力障碍直接相关
PNAS：噪音影响婴幼儿听力和智力发育
生物谷推荐原始出处：
The American Journal of Human Genetics, Volume 85, Issue 6, 809-822, 11 December 2009
Dosage-Dependent Severity of the Phenotype in Patients with Mental Retardation Due to a Recurrent Copy-Number Gain at Xq28 Mediated by an Unusual Recombination
Joke Vandewalle1, 2, 9, Hilde Van Esch3, 9, Karen Govaerts1, 2, Jelle Verbeeck1, 2, Christiane Zweier4, Irene Madrigal5, Montserrat Mila5, Elly Pijkels3, Isabel Fernandez6, Jürgen Kohlhase7, Christiane Spaich8, Anita Rauch4, Jean-Pierre Fryns3, Peter Marynen1, 2 and Guy Froyen1, 2, ,
1 Human Genome Laboratory, Department for Molecular and Developmental Genetics, VIB, B-3000 Leuven, Belgium
2 Human Genome Laboratory, Center for Human Genetics, K.U. Leuven, B-3000 Leuven, Belgium
3 Center for Human Genetics, University Hospital Leuven, K.U. Leuven, B-3000 Leuven, Belgium
4 Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, D-91054 Erlangen, Germany
5 Biochemistry and Molecular Genetics Department Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer and CIBERER, 08036 Barcelona, Spain
6 Instituto de Biología y Genética Molecular, Universidad de Valladolid, 47003 Valladolid, Spain
7 Center for Human Genetics Freiburg, D-79106 Freiburg, Germany
8 Institute for Clinical Genetics, Olgahospital, D-70176 Stuttgart, Germany
We report on the identification of a 0.3 Mb inherited recurrent but variable copy-number gain at Xq28 in affected males of four unrelated families with X-linked mental retardation (MR). All aberrations segregate with the disease in the families, and the carrier mothers show nonrandom X chromosome inactivation. Tiling Xq28-region-specific oligo array revealed that all aberrations start at the beginning of the low copy repeat LCR-K1, at position 153.20 Mb, and end just distal to LCR-L2, at 153.54 Mb. The copy-number gain always includes 18 annotated genes, of which RPL10, ATP6AP1 and GDI1 are highly expressed in brain. From these, GDI1 is the most likely candidate gene. Its copy number correlates with the severity of clinical features, because it is duplicated in one family with nonsyndromic moderate MR, is triplicated in males from two families with mild MR and additional features, and is present in five copies in a fourth family with a severe syndromic form of MR. Moreover, expression analysis revealed copy-number-dependent increased mRNA levels in affected patients compared to control individuals. Interestingly, analysis of the breakpoint regions suggests a recombination mechanism that involves two adjacent but different sets of low copy repeats. Taken together, our data strongly suggest that an increased expression of GDI1 results in impaired cognition in a dosage-dependent manner. Moreover, these data also imply that a copy-number gain of an individual gene present in the larger genomic aberration that leads to the severe MECP2 duplication syndrome can of itself result in a clinical phenotype as well.
