小说在ADRBK1突变的识别在一个家族和一个常染色体显性小脑性共济失调(P6.402)

文摘

目的:一种新的基因突变负责家族的独特的表型与常染色体显性小脑性共济失调(ADCA)。背景:ADCA家族有一个独特的表型,以缓慢的进步小脑性共济失调和构音障碍没有extra-oculomotor异常。所有已知的基因突变ADCA没有在临床检查中发现。这提出了一种新的突变的可能性。方法:所有现存的渊源者的家庭成员被邀请参加。十个科目包括提供的渊源者同意。所有的受试者都接受临床检查,MRI脑部扫描和血液收集。从全血中提取DNA样本柯灵医学研究机构的,悉尼和DNA样本被送往美国国立卫生研究院(NIH)的全外显子组测序和分析。每个个体的外显子组测序经历了几个生物过滤步骤来识别潜在的变体。首先,他们在NIH对齐对当地的基因组数据库和参考人类基因组19。 Those potential variants that were previously identified in the 1000 Genome Project were excluded in the second filtering step. Thirdly, the remaining potential variants were manually inspected by using Integrative Genomics Viewer. The fourth filtering step was to identify the variants present in the known symptomatic subjects and absent in the asymptomatic subjects. All remaining potential variants were validated by Sanger Sequencing and their protein coding effects predicted by using SeattleSeq Annotation. RESULTS: Mutated ADRBK1 was the only possible genetic mutation that was responsible for this unique phenotype of ADCA. Sanger sequencing identified the mutation was due to an amino acid change from ATT (Isoleucine) to ATG (Methionine) at amino acid position 140. CONCLUSIONS: Mutated ADRBK1 is likely to be responsible for this kindred with ADCA with unique phenotype. However, further functional studies of this gene is required to confirm this finding.

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