Martínez Francisco, Martínez-Garay Isabel, Oltra Silvestre, Moltó María Dolores, Orellana Carmen, Monfort Sandra, Prieto Félix, Tejada Isabel
Unidad de Genética, Hospital La Fe, Valencia, Spain.
Am J Med Genet A. 2004 Dec 1;131(2):174-8. doi: 10.1002/ajmg.a.30352.
Clinical and molecular studies are reported on a Basque family (MRX82) with nonsyndromic X-linked mental retardation (XLMR) in five affected males. A total of 38 microsatellite markers were typed. The XLMR locus has been linked to DXS8067, DXS1001, DXS425, DXS7877, and DXS1183 with a maximum LOD score of 2.4. The haplotype studies and multipoint linkage analysis suggest a localization of the MRX82 locus to an interval of 7.6 Mb defined by markers DXS6805 and DXS7346, in Xq24 and Xq25, respectively. No gene contained in this interval has been so far associated with nonsyndromic mental retardation, except for GRIA3, disrupted by a balanced translocation in a female patient with bipolar affective disorder and mental retardation. However, the search for mutations of this gene did not showed a pathogenic mutation in the present family. Given that there are other eight MRX families overlapping this interval, none of them with known mutation, we conclude that at least one new gene responsible for nonsyndromic mental retardation is located in this region.
报道了一个患有非综合征性X连锁智力障碍（XLMR）的巴斯克家族（MRX82）中5名患病男性的临床和分子研究。共对38个微卫星标记进行了分型。XLMR基因座已与DXS8067、DXS1001、DXS425、DXS7877和DXS1183连锁，最大对数优势分数为2.4。单倍型研究和多点连锁分析表明，MRX82基因座定位于分别由Xq24和Xq25中的标记DXS6805和DXS7346定义的7.6 Mb区间。到目前为止，该区间内除GRIA3外没有基因与非综合征性智力障碍相关，GRIA3在一名患有双相情感障碍和智力障碍的女性患者中因平衡易位而中断。然而，对该基因的突变搜索在本家族中未发现致病突变。鉴于有其他8个MRX家族与该区间重叠，且均无已知突变，我们得出结论，该区域至少存在一个导致非综合征性智力障碍的新基因。
