一个轻型智力发育迟缓家族中异常ATP依赖的Lon蛋白酶基因突变
A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation作者机构：Ctr. for Hum. Genet./Child Neurol. Mid-Hudson Family Health Institute 279 Main St . New Paltz NY 12561 United States Dr.
出 版 物：《世界核心医学期刊文摘（神经病学分册）》 (Digest of the World Core Medical Journals:Clinical Neurology)
年 卷 期：2005年第1卷第5期
页 面：33-33页
学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学]
主 题：智力发育迟缓 ATP Lon 基因突变 认知障碍 线粒体复制 蛋白谱 无义突变 终止密码子 长时程增强
摘 要：Background: Identifying the genetic factors that contribute to memory and lea rning is limited by the complexity of brain development and the lack of suitable human models for mild disorders of cognition. Methods: Previously, a disease lo cus was mapped for a mild type of nonsyndromic mental retardation (IQ between 50 and 70) to a 4.2-MB interval on chromosome 3p25-pter in a large kindred. Th e genes and transcripts within the candidate region were systematically analyzed for mutations by single-strand polymorphism analysis and DNA sequencing. Resu lts: A nonsense mutation causing a premature stop codon in a novel gene (cereblo n; CRBN) was identified that encodes for an ATP-dependent Lon protease. The pr edicted protein sequence is highly conserved across species, and it belongs to a family of proteins that selectively degrade short-lived polypeptides and regu late mitochondrial replication and transcription. One member of the Lon-contai ning protein family is regionally expressed in the human hippocampus, an importa nt neuroanatomic region that is involved in long-term potentiation and learnin g. The mutation in the CRBN gene described interrupts an N-myristoylation site and eliminates a casein kinase II phosphorylation site at the C terminus. Concl usions: A gene on chromosome 3p that is associated with mild mental retardation in a large kindred is reported. This finding implicates a role for the ATP-dep endent degradation of proteins in memory and learning.
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