Mutations in the gene encoding the sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation
Mutations in the gene encoding the sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation
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DOI：
10.1086/510137
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发表时间：
2006-12-01
影响因子：
9.8
通讯作者：
Raymond, F. Lucy
中科院分区：
文献类型：
--
作者：
Tarpey, Patrick S.;Stevens, Claire;Raymond, F. Lucy
在对250个X连锁智力低下（XLMR）家族的X染色体编码外显子进行系统测序筛选中，我们在三个家族的Xp22上发现了两个无义突变和一个一致剪接位点突变。这些家庭中受影响的个体表现出轻度到重度的智力迟钝。其他特征包括生命早期张力过低和行走迟缓。AP1S2编码一种适应蛋白，该适应蛋白是在位于高尔基复合体的包被囊泡的细胞质表面发现的适应蛋白复合体的一部分。该复合物介导网格蛋白向囊泡膜的募集。在三个受xlmr影响的家族中发现的AP1S2突变可能会导致接头蛋白复合物的破坏，从而导致异常的内吞噬过程，这种缺陷可能会导致突触发育和功能异常。AP1S2是第一个报道的编码直接参与内吞囊泡组装的蛋白质的XLMR基因。
In a systematic sequencing screen of the coding exons of the X chromosome in 250 families with X-linked mental retardation (XLMR), we identified two nonsense mutations and one consensus splice-site mutation in the AP1S2 gene on Xp22 in three families. Affected individuals in these families showed mild-to-profound mental retardation. Other features included hypotonia early in life and delay in walking. AP1S2 encodes an adaptin protein that constitutes part of the adaptor protein complex found at the cytoplasmic face of coated vesicles located at the Golgi complex. The complex mediates the recruitment of clathrin to the vesicle membrane. Aberrant endocytic processing through disruption of adaptor protein complexes is likely to result from the AP1S2 mutations identified in the three XLMR-affected families, and such defects may plausibly cause abnormal synaptic development and function. AP1S2 is the first reported XLMR gene that encodes a protein directly involved in the assembly of endocytic vesicles.