Loss of ZDHHC15 expression in a woman with a balanced translocation t(X;15)(q13.3;cen) and severe mental retardation
Loss of ZDHHC15 expression in a woman with a balanced translocation t(X;15)(q13.3;cen) and severe mental retardation
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DOI：
10.1038/sj.ejhg.5201445
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发表时间：
2005-08-01
影响因子：
5.2
通讯作者：
Dahl, N
中科院分区：
文献类型：
--
作者：
Mansouri, MR;Marklund, L;Dahl, N
X-连锁精神发育迟滞(XLMR)影响着600名男性中的一名，并且是高度异质性的。我们在这里描述了一位29岁的女性，患有严重的非综合征性智力低下，并在X和15染色体之间平衡互换易位[46，XX，t(X；15)(q13.3；cen)]。甲基化研究显示，患者来源的淋巴细胞中有100%扭曲的X-失活，表明正常的X染色体保持不活跃。断点的物理定位将Xq13.3断点定位在ZDHHC15基因第一外显子的3.9kb以内，该外显子编码一个锌指和一个含有DHHC结构域的产物。表达分析表明，该基因的不同转录变体在大脑中表达。对患者淋巴细胞的ZDHHC15特异性RT-PCR分析显示，在对照样本中检测到ZDHHC15转录本变体。我们认为，该患者中ZDHHC15转录本的缺失与她的表型有关，该基因是非综合征XLMR的有力候选基因。
X-linked mental retardation ( XLMR) affects one in 600 males and is highly heterogeneous. We describe here a 29-year-old woman with severe nonsyndromic mental retardation and a balanced reciprocal translocation between chromosomes X and 15 [ 46, XX, t( X; 15)( q13.3; cen)]. Methylation studies showed a 100% skewed X-inactivation in patient-derived lymphocytes indicating that the normal chromosome X is retained inactive. Physical mapping of the breakpoints localised the Xq13.3 breakpoint to within 3.9 kb of the first exon of the ZDHHC15 gene encoding a zinc-finger and a DHHC domain containing product. Expression analysis revealed that different transcript variants of the gene are expressed in brain. ZDHHC15-specific RT-PCR analysis on lymphocytes from the patient revealed an absence of ZDHHC15 transcript variants, detected in control samples. We suggest that the absence of the ZDHHC15 transcripts in this patient contributes to her phenotype, and that the gene is a strong candidate for nonsyndromic XLMR.