International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ward, Tokyo, 162-8666, Japan.
Genomics. 2009 Dec;94(6):414-22. doi: 10.1016/j.ygeno.2009.08.015. Epub 2009 Sep 3.
A novel microdeletion of 14q13.1q13.3 was identified in a patient with developmental delay and intractable epilepsy. The 2.2-Mb deletion included 15 genes, of which TULIP1 (approved gene symbol: RALGAPA1)was the only gene highly expressed in the brain. Western blotting revealed reduced amount of TULIP1 in cell lysates derived from immortalized lymphocytes of the patient, suggesting the association between TULIP1 haploinsufficiency and the patient's phenotype, then 140 patients were screened for TULIP1 mutations and four missense mutations were identified. Although all four missense mutations were common with parents, reduced TULIP1 was observed in the cell lysates with a P297T mutation identified in a conserved region among species. A full-length homolog of human TULIP1 was identified in zebrafish with 72% identity to human. Tulip1 was highly expressed in zebrafish brain, and knockdown of which resulted in brain developmental delay. Therefore, we suggest that TULIP1 is a candidate gene for developmental delay.
在一名患有发育迟缓伴难治性癫痫的患者中发现了一个新的 14q13.1q13.3 微缺失。该 2.2Mb 缺失包括 15 个基因，其中 TULIP1（已批准的基因符号：RALGAPA1）是唯一在大脑中高度表达的基因。Western blot 分析显示，患者永生化淋巴细胞裂解物中 TULIP1 含量减少，提示 TULIP1 杂合不足与患者表型之间存在关联，随后对 140 名患者进行了 TULIP1 突变筛查，发现了 4 个错义突变。尽管所有 4 个错义突变在父母中均常见，但在细胞裂解物中观察到 TULIP1 减少，其中在物种间保守区域鉴定出 P297T 突变。在斑马鱼中鉴定出与人 TULIP1 具有 72%同一性的全长同源物。Tulip1 在斑马鱼大脑中高度表达，敲低其表达导致大脑发育迟缓。因此，我们认为 TULIP1 是发育迟缓的候选基因。
