A mutation in RYK is a genetic factor for nonsyndromic cleft lip and palate
A mutation in RYK is a genetic factor for nonsyndromic cleft lip and palate
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DOI：
10.1597/04-145.1
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发表时间：
2006-05-01
期刊：
影响因子：
--
通讯作者：
Yoshiura, Koh-ichiro
中科院分区：
文献类型：
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作者：
Watanabe, Akira;Akita, Sadanori;Yoshiura, Koh-ichiro
目的：RYK、EPHB 2和EPHB 3基因是唇腭裂和/或单纯腭裂发病机制的有吸引力的候选基因。Ryk缺陷小鼠和Ephb 2/Ephb 3（与RYK相互作用分子的基因）双突变小鼠均显示chipalpalpate.Setting：在大量日本和越南唇腭裂和/或腭裂和腭裂患者中进行RYK、EPHB 2和EPHB 3的突变搜索。结果：在1例越南唇腭裂患者的RYK基因中发现1个错义突变，即1355 G>A（Y 452 C）。在1646名越南人、日本人和高加索人中未发现这种突变，其中包括354名唇腭裂和/或单纯腭裂患者。克隆形成实验表明，与野生型RYK相比，突变型RYK的蛋白活性显著降低，表明RYK的转化能力被该突变所削弱。虽然病例对照研究和三个单独的单核苷酸多态性的传播不平衡测试提供了与口腔裂的关联没有证据，一个罕见的单倍型的病例对照研究表明，在日本唇腭裂和/或腭裂患者和腭裂只有正相关。结论：错义突变1355 G>A和一种罕见的单核苷酸多态性单倍型可能与越南人唇腭裂的发生有关，而与日本人唇腭裂的发生有关。
Objective: The RYK, EPHB2, and EPHB3 genes are attractive candidates for cleft lip and/or palate and cleft palate only pathogenesis. Both the Ryk-deficient mouse and Ephb2/Ephb3 (genes for interaction molecules with RYK) double-mutant mouse show cleft palate.Setting: Mutation searches for RYK, EPHB2, and EPHB3 were carried out in a large number of Japanese and Vietnamese patients with cleft lip and/or palate and cleft palate only. Case-control study and transmission disequilibrium tests were performed also, using three single nucleotide polymorphisms within a linkage disequilibrium block in RYX Seven haplotypes were constructed from the single nucleotide polymorphisms.Results: A missense mutation, 1355G>A (Y452C), in RYK was identified in one Vietnamese patient with cleft lip and/or palate. This mutation was not found among 1646 Vietnamese, Japanese, and Caucasians, including 354 cleft lip and/ or palate and cleft palate only patients. Colony formation assay using NIH3T3 cells transfected with mutant cDNA revealed that mutant RYK had significantly reduced protein activity, compared with those with wild-type RYK, implying that the transformation ability of RYK is depleted by this mutation. Although a case-control study and transmission disequilibrium tests on three individual single nucleotide polymorphisms provided no evidence for association with oral clefts, a case-control study on one rare haplotype suggested a positive association in Japanese patients with cleft lip and/or palate and cleft palate only. No mutations in EPHB2 and EPHB3 were found in any patients examined.Conclusion: The findings suggested that a missense mutation, 1355G>A, and one rare single nucleotide polymorphisms haplotype may play a role in the development of cleft lip and/or palate in the Vietnamese, and cleft lip and/ or palate and cleft palate only in the Japanese.