由来自加州大学圣地亚哥大学和耶鲁大学医学院的研究人员领导的国际合作团队鉴定到BCKDK(支链酮酸脱氢酶激酶)基因的失活性突变会引起带有癫痫症状的自闭症,他们发现这种自闭症可通过补充营养而得以治疗。

-2012年10月19日《科学》

中文翻译


【题目】BCKD激酶突变导致的自闭症可通过营养补充剂而得以治疗

【译文】自闭症谱系障碍是一种遗传性的多相综合征,其特点是社会互动障碍。目前的躯体治疗手段缺乏有效的疗效。本研究在患有自闭症、癫痫和智力障碍的同血缘家族成员中鉴定到BCKDK(支链酮酸脱氢酶激酶)基因发生失活性突变。该基因编码的蛋白质的磷酸化作用使得支链酮酸脱氢酶(BCKDH)的E1α亚基失活。自闭症患者带有纯合的BCKDK突变,其体内的BCKDK信使RNA和蛋白质、E1α磷酸化作用和血浆支链氨基酸含量都降低。Bckdk敲除小鼠表现出异常的大脑氨基酸谱和不能响应食物补充的神经行为缺陷。总之,自闭症表现出的智力障碍和癫痫症状是由BCKDK基因突变引起的,这是潜在可治疗的综合征的特点。

英文原稿


[Title]: Mutations in BCKD-kinase Lead to a Potentially Treatable Form of Autism with Epilepsy

[Authors]: Gaia Novarino, Paul El-Fishawy, Hulya Kayserili, Nagwa A. Meguid, Eric M. Scott, Jana Schroth, Jennifer L. Silhavy, Majdi Kara, Rehab O. Khalil, Tawfeg Ben-Omran, A. Gulhan Ercan-Sencicek, Adel F. Hashish, Stephan J. Sanders, Abha R. Gupta, Hebatalla S. Hashem, Dietrich Matern, Stacey Gabriel, Larry Sweetman, Yasmeen Rahimi, Robert A. Harris, Matthew W. State, and Joseph G. Gleeson

[Abstract]:Autism spectrum disorders are a genetically heterogeneous constellation of syndromes characterized by impairments in reciprocal social interaction. Available somatic treatments have limited efficacy. We have identified inactivating mutations in the gene BCKDK (Branched Chain Ketoacid Dehydrogenase Kinase) in consanguineous families with autism, epilepsy, and intellectual disability. The encoded protein is responsible for phosphorylation-mediated inactivation of the E1α subunit of branched-chain ketoacid dehydrogenase (BCKDH). Patients with homozygous BCKDK mutations display reductions in BCKDK messenger RNA and protein, E1α phosphorylation, and plasma branched-chain amino acids. Bckdk knockout mice show abnormal brain amino acid profiles and neurobehavioral deficits that respond to dietary supplementation. Thus, autism presenting with intellectual disability and epilepsy caused by BCKDK mutations represents a potentially treatable syndrome.

原文地址

http://www.sciencemag.org/content/338/6105/394.short

 

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