...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The American Journal of Human Genetics >Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature.
【24h】

Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature.

机译：衔接蛋白复合物4缺乏会导致严重的常染色体隐性智力障碍，进行性痉挛性截瘫，性格害羞和身材矮小。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Intellectual disability inherited in an autosomal-recessive fashion represents an important fraction of severe cognitive-dysfunction disorders. Yet, the extreme heterogeneity of these conditions markedly hampers gene identification. Here, we report on eight affected individuals who were from three consanguineous families and presented with severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. Using a combination of autozygosity mapping and either Sanger sequencing of candidate genes or next-generation exome sequencing, we identified one mutation in each of three genes encoding adaptor protein complex 4 (AP4) subunits: a nonsense mutation in AP4S1 (NM_007077.3: c.124C>T, p.Arg42( *)), a frameshift mutation in AP4B1 (NM_006594.2: c.487_488insTAT, p.Glu163_Ser739delinsVal), and a splice mutation in AP4E1 (NM_007347.3: c.542+1_542+4delGTAA, r.421_542del, p.Glu181Glyfs( *)20). Adaptor protein complexes (AP1-4) are ubiquitously expressed, evolutionarily conserved heterotetrameric complexes that mediate different types of vesicle formation and the selection of cargo molecules for inclusion into these vesicles. Interestingly, two mutations affecting AP4M1 and AP4E1 have recently been found to cause cerebral palsy associated with severe intellectual disability. Combined with previous observations, these results support the hypothesis that AP4-complex-mediated trafficking plays a crucial role in brain development and functioning and demonstrate the existence of a clinically recognizable syndrome due to deficiency of the AP4 complex.
机译：以常染色体隐性方式遗传的智力残疾是严重认知功能障碍的重要组成部分。然而，这些条件的极端异质性明显阻碍了基因鉴定。在这里，我们报告了来自三个近血缘家族的八位受影响的个体，这些个体患有严重的智力障碍，语言缺失，害羞的性格，刻板的笑声，肌张力减退，发展为痉挛性截瘫，小头畸形，足部畸形，下肢肌肉质量下降，无法走路和发育迟缓。结合使用自动纯合作图和候选基因的Sanger测序或下一代外显子组测序的组合，我们在编码衔接子蛋白复合物4（AP4）亚基的三个基因的每一个中鉴定出一个突变：AP4S1中的无意义突变（NM_007077.3：c .124C> T，p.Arg42（*）），AP4B1中的移码突变（NM_006594.2：c.487_488insTAT，p.Glu163_Ser739delinsVal）和AP4E1中的剪接突变（NM_007347.3：c.542 + 1_542 + 4delGTAA ，r.421_542del，p.Glu181Glyfs（*）20）。衔接蛋白复合物（AP1-4）被普遍表达，在进化上保守的异四聚体复合物，介导不同类型的囊泡形成和选择包含在这些囊泡中的货物分子。有趣的是，最近发现影响AP4M1和AP4E1的两个突变会导致与严重智力障碍相关的脑瘫。结合先前的观察结果，这些结果支持以下假设：AP4复合物介导的运输在脑发育和功能中起着至关重要的作用，并证明由于AP4复合物的缺乏而存在临床上可识别的综合征。

著录项

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号