Analysis of NOD-like receptor NLRP1 in multiple sclerosis families
Analysis of NOD-like receptor NLRP1 in multiple sclerosis families
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DOI：
10.1007/s00251-017-1034-2
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发表时间：
2018-03-01
期刊：
影响因子：
3.2
通讯作者：
Vilarino-Gueell, Carles
中科院分区：
文献类型：
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作者：
Bernales, Cecily Q.;Encarnacion, Mary;Vilarino-Gueell, Carles
外显子组测序技术的实施已经开始揭开家族性多发性硬化症(MS)的遗传病因。NLRP1中的一个纯合子p.G587S突变被认为是一对受影响的同胞中MS发病的潜在原因，后者后来发展为恶性黑色素瘤。为了验证隐性NLRP1突变在MS病理机制中的作用，我们检查了来自加拿大的326名MS患者的外显子组测序数据，以识别NLRP1错义和无义变体。这项分析没有确认先前描述的p.G587S突变；但是，观察到三名可能存在NLRP1复合杂合子突变的患者。单倍型和分离分析表明，在这些患者中观察到的变异是顺式遗传的，并不与家族内的疾病分离。因此，对来自加拿大的多发性硬化症患者的分析未能确定NLRP1的潜在致病突变，包括前面描述的p.G587S突变。需要进一步的研究来确认NLRP1在MS的病理生理学中的作用。
The implementation of exome sequencing technologies has started to unravel the genetic etiology of familial multiple sclerosis (MS). A homozygote p.G587S mutation in NLRP1 has been suggested as potentially causative for the onset of MS in an affected sibling pair, who later developed malignant melanoma. To validate the proposed role of recessive NLRP1 mutations in the pathological mechanisms of MS, we examined exome sequencing data from 326 MS patients from Canada for the identification of NLRP1 missense and nonsense variants. This analysis did not identify the previously described p.G587S mutation; however, three patients with potential NLRP1 compound heterozygote mutations were observed. Haplotype and segregation analyses indicate that the variants observed in these patients were inherited in cis, and do not segregate with disease within families. Thus, the analysis of MS patients from Canada failed to identify potentially pathogenic mutations in NLRP1, including the previously described p.G587S mutation. Further studies are necessary to confirm a role of NLRP1 in the pathophysiology of MS.