Tarpey Patrick S, Stevens Claire, Teague Jon, Edkins Sarah, O'Meara Sarah, Avis Tim, Barthorpe Syd, Buck Gemma, Butler Adam, Cole Jennifer, Dicks Ed, Gray Kristian, Halliday Kelly, Harrison Rachel, Hills Katy, Hinton Jonathon, Jones David, Menzies Andrew, Mironenko Tatiana, Perry Janet, Raine Keiran, Richardson David, Shepherd Rebecca, Small Alexandra, Tofts Calli, Varian Jennifer, West Sofie, Widaa Sara, Yates Andy, Catford Rachael, Butler Julia, Mallya Uma, Moon Jenny, Luo Ying, Dorkins Huw, Thompson Deborah, Easton Douglas F, Wooster Richard, Bobrow Martin, Carpenter Nancy, Simensen Richard J, Schwartz Charles E, Stevenson Roger E, Turner Gillian, Partington Michael, Gecz Jozef, Stratton Michael R, Futreal P Andrew, Raymond F Lucy
Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Am J Hum Genet. 2006 Dec;79(6):1119-24. doi: 10.1086/510137. Epub 2006 Nov 1.
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.
在对250个患有X连锁智力障碍（XLMR）家庭的X染色体编码外显子进行的系统测序筛查中，我们在三个家庭的Xp22上的AP1S2基因中鉴定出两个无义突变和一个共有剪接位点突变。这些家庭中的受影响个体表现出轻度至重度智力障碍。其他特征包括生命早期肌张力减退和行走延迟。AP1S2编码一种衔接蛋白，该蛋白是位于高尔基体复合体包被小泡胞质面的衔接蛋白复合体的一部分。该复合体介导网格蛋白募集到小泡膜上。在三个受XLMR影响的家庭中鉴定出的AP1S2突变可能导致通过衔接蛋白复合体破坏而产生异常的内吞加工，并且这种缺陷可能合理地导致异常的突触发育和功能。AP1S2是第一个报道的XLMR基因，其编码直接参与内吞小泡组装的蛋白质。
