The CASK gene harbored in a deletion detected by array-CGH as a potential candidate for a gene causative of X-linked dominant mental retardation
The CASK gene harbored in a deletion detected by array-CGH as a potential candidate for a gene causative of X-linked dominant mental retardation
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DOI：
10.1002/ajmg.a.32433
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发表时间：
2008-08-15
影响因子：
2
通讯作者：
Inazawa, Johji
中科院分区：
文献类型：
--
作者：
Hayashi, Shin;Mizuno, Seiji;Inazawa, Johji
在这里，我们报告一名5岁的日本女孩，患有发育障碍和小头畸形。尽管她有正常的核型，但基于细菌人工染色体阵列的比较基因组杂交分析发现，Xp11.3-p11.4处存在新的4.0-Mb杂合缺失，包含9个基因。相比之下，在同一地区，患有非典型诺里病男孩的健康携带者母亲的缺失率较小。我们排除了四个基因作为候选基因，这些基因的单倍性不足会导致发育迟缓。在其他五个基因中，CASK似乎是最有可能成为致病基因的候选基因，因为它在胎儿大脑中强烈表达，并在神经发育和突触功能中发挥重要作用。我们证实，与健康对照组相比，患者CaskmRNA的表达减少，患者的X染色体失活没有偏斜。这些结果表明，CAASK基因缺失导致单倍体功能不全，这可能是患者发育迟缓或智力低下的原因。(C)2008年Wiley-Liss，Inc.
Here we report on a 5-year-old Japanese girl with developmental dealy and microcephaly. Although she had a normal karyotype, a bacterial artifical chromosome-based array-comparative genome hybridization analysis detected a de novo 4.0-Mb heterozygous deletion at Xp11.3-p11.4 harboring nine genes. By comparison with a healthy carrier mother of a boy with atypical Norrie disease having a smaller deletion in the same region. we excluded four genes as candidates whose haploinsufficiency would be causative for developmental delay. Among the other five genes, CASK seems to be the most likely candidate for a causative gene, because it is strongly expressed in fetal brain and plays important roles in neural development and synaptic function. We confirmed that the expression of CASK mRNA was decreased in the patient compared with healthy controls and the patient's X-chromosomal inactivation was not skewed. These results suggested that the genetic deletion of CASK results in haploinsufficiency, which might be causative for the patient's developmental delay or mental retardation. (C) 2008 Wiley-Liss, Inc.