L1综合征临床表型研究及突变分析

IF 1.8 Q4 NEUROSCIENCES
Madhan Shrinivasamurthy, Shreeshail V Benakanal, Nagaraj Kakanahalli
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引用次数: 0

摘要

L1CAM蛋白在早期发育过程中起着至关重要的作用,L1CAM突变导致L1综合征。L1综合征在家族内部和家族之间的表现差异很大。L1综合征的临床症状包括智力低下、脑积水、痉挛、失语和拇指内收。发现L1CAM基因突变会影响L1胞外区结构上必需的关键残基,导致蛋白质结合特性的改变。在大多数情况下,这些突变会产生意想不到的表型,需要彻底了解。目的通过智力迟钝、脑积水、失语、痉挛、拇指内收等多种表型对L1综合征患者进行鉴别,并对有三种以上症状的患者或智力迟钝(MR)患儿进行鉴别。本研究旨在通过Sanger测序筛选多个外显子的突变。方法本研究采用针对L1CAM基因特定外显子设计的引物对扩增产物进行扩增和测序,通过Sanger测序检测L1综合征患者的突变。使用卡方检验确定突变检出率与L1综合征表型的数量,并使用几个计算机程序来研究变异的潜在影响。结果6例患者存在9种不同的突变。具有1种以上L1综合征表型和家族中有1人以上患者的突变检出率(83.33%)高于单一表型和阴性家族史患者(16.6%)。结论突变检出率与典型L1综合征表型的存在及家族史有关。在印度人群中筛选L1 cam基因突变是分析突变和了解L1疾病的潜在机制的必要条件。本研究发现了一些新的突变,这些突变与发育过程中各种生物学功能的改变有关,从而导致L1综合征的发病机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Study of Clinical Phenotypes and Analysis of Mutations in L1 Syndrome
Background L1CAM protein plays a crucial role during early development and mutations in L1CAM cause L1 syndrome. L1 syndrome demonstrates a highly variable presentation within and between families. The clinical symptoms of L1 syndrome include mental retardation, hydrocephalus, spasticity, aphasia, and adducted thumb. Mutations in L1CAM gene were found to affect structurally essential key residues in extracellular region of L1 leading to changes in protein binding properties. In most cases, these mutations create unexpected phenotypes which need to be understood thoroughly. Purpose The L1 syndrome patients were identified by various phenotypes like mental retardation, hydrocephalus, aphasia, spasticity, adducted thumb, etc., and the patients or mental retardation (MR) children who had more than three symptoms. This study aimed to screen mutations in multiple exons by Sanger sequencing. Methods The present study employed primers which are designed for specific exons of L1CAM gene to amplify and sequence the amplified product to detect the mutations in L1 syndrome patients by the Sanger sequencing. Chi-square test was used to determine the mutation detection rate with the number of L1 syndrome phenotypes and several i n silico programs were used to investigate potential effects of the variants. Results The nine different mutations in six patients. The mutation detection rate was high (83.33%) in patients with more than one L1 syndrome phenotype and in patients with more than one affected member in a family compared to patients with single phenotypes and negative family history (16.6%). Conclusion The mutation detection rate was related to the presence of typical L1 syndrome phenotypes and the family history. Screening of L1CAM gene mutations in the Indian population is much needed to analyze the mutations and understand the mechanism underlying L1 disease. The present study has identified some novel mutations which are implicated in alterations in various biological functions during development leading to pathogenesis of L1 syndrome.
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来源期刊
Annals of Neurosciences
Annals of Neurosciences NEUROSCIENCES-
CiteScore
2.40
自引率
0.00%
发文量
39
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