Molecular characterization of congenital myasthenic syndromes in Spain
Molecular characterization of congenital myasthenic syndromes in Spain
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DOI：
10.1016/j.nmd.2017.08.003
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发表时间：
2017-12-01
影响因子：
2.8
通讯作者：
Nascimento, A.
中科院分区：
文献类型：
--
作者：
Natera-de Benito, D.;Topf, A.;Nascimento, A.
先天性肌无力综合征(CMS)是一组异质性的遗传性疾病，所有这些疾病都会损害神经肌肉传递。流行病学数据和基因突变的频率在文献中很少。在这里，我们描述了来自西班牙的64例经基因确认的CMS患者的分子遗传学和临床表现。在我们的患者中发现了36个CHRNE、RAPSN、COLQ、GFPT1、DOK7、CHRNG、GMPPB、ChAT、CHRNA1和CHRNB1基因突变，其中5个基因到目前为止还没有报道。这些数据概述了不同CMS亚型在大量西班牙人中的相对频率。CHRNE突变是西班牙CMS最常见的原因，占总数的27%。第二种最常见的是RAPSN突变。我们发现与其他人群相比，GFPT1突变率更高：值得注意的是，几个创始人突变对西班牙的CMS有很大贡献：RAPSN c.264C>；A(p.Asn88Lys)，CHRNE c.130insG(Glu44Glyfs*3)，CHRNE c.1353insG(p.Asn542Gluf*4)，DOK7 c.1124_1127 dup(p.Ala378Serfs*30)，与其他人群相比，西班牙的CMS尤其频繁，COLQ c.1289A>；C(p.Tyr430Ser)。此外，我们描述了与不同CMS基因相关的表型和区分临床体征，这可能有助于识别特定的CMS亚型以指导诊断和治疗。(C)2017爱思唯尔B.V.保留所有权利。
Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders, all of which impair neuromuscular transmission. Epidemiological data and frequencies of gene mutations are scarce in the literature. Here we describe the molecular genetic and clinical findings of sixty-four genetically confirmed CMS patients from Spain. Thirty-six mutations in the CHRNE, RAPSN, COLQ, GFPT1, DOK7, CHRNG, GMPPB, CHAT, CHRNA1, and CHRNB1 genes were identified in our patients, with five of them not reported so far.. These data provide an overview on the relative frequencies of the different CMS subtypes in a large Spanish population. CHRNE mutations are the most common cause of CMS in Spain, accounting for 27% of the total. The second most common are RAPSN mutations. We found a higher rate of GFPT1 mutations in comparison with other populations: Remarkably, several founder mutations made a large contribution to CMS in Spain: RAPSN c.264C > A (p.Asn88Lys), CHRNE c.130insG (Glu44Glyfs*3), CHRNE c.1353insG (p.Asn542Gluf*4), DOK7 c.1124_1127dup (p.Ala378Serfs*30), and particularly frequent in Spain in comparison with other populations, COLQ c.1289A > C (p.Tyr430Ser). Furthermore, we describe phenotypes and distinguishing clinical signs associated with the various CMS genes which might help to identify specific CMS subtypes to guide diagnosis and management. (C) 2017 Elsevier B.V. All rights reserved.