Mutations in the BRWD3 gene cause X-linked mental retardation associated with macrocephaly
Mutations in the BRWD3 gene cause X-linked mental retardation associated with macrocephaly
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DOI：
10.1086/520677
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发表时间：
2007-08-01
影响因子：
9.8
通讯作者：
Raymond, F. Lucy
中科院分区：
文献类型：
--
作者：
Field, Michael;Tarpey, Patrick S.;Raymond, F. Lucy
在对 250 个非综合征性 X 连锁智力低下 (XLMR) 家族的 X 染色体编码序列进行系统筛查的过程中，发现两个家族存在 BRWD3 截短突变，BRWD3 是编码含溴结构域和 WD 重复结构域的蛋白质的基因。在这两个家族中，突变与受影响的男性的表型分离。受影响的男性患有巨头畸形，前额突出、大杯形耳朵和轻度至中度智力障碍。在 520 条对照 X 染色体中未发现截短变异。因此，BRWD3 是一种与巨头畸形相关的 XLMR 病因学有关的新基因，可能通过改变影响细胞增殖的细胞内信号传导途径而引起疾病。
In the course of systematic screening of the X-chromosome coding sequences in 250 families with nonsyndromic X-linked mental retardation (XLMR), two families were identified with truncating mutations in BRWD3, a gene encoding a bromodomain and WD-repeat domain-containing protein. In both families, the mutation segregates with the phenotype in affected males. Affected males have macrocephaly with a prominent forehead, large cupped ears, and mild-to-moderate intellectual disability. No truncating variants were found in 520 control X chromosomes. BRWD3 is therefore a new gene implicated in the etiology of XLMR associated with macrocephaly and may cause disease by altering intracellular signaling pathways affecting cellular proliferation.