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首页> 外文期刊>Human Genomics >Genetic studies of Polish migraine patients: screening for causative mutations in four migraine-associated genes
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Genetic studies of Polish migraine patients: screening for causative mutations in four migraine-associated genes

机译：波兰偏头痛患者的遗传研究：筛选四个偏头痛相关基因的致病性突变

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Background and aim Migraine is the most common neurological disorder, affecting approximately 12?% of the adult population worldwide, caused by both environmental and genetic factors. Three causative genes have been identified in familial hemiplegic migraine (FHM) families: CACNA1A , ATP1A2 , and SCNA1A . Recently, several mutations in KCNK18 have also been found as causative factors in migraine development. The aim of our study was to identify the genetic background of migraine in the Polish population. Material and methods Sixty patients with migraine without aura (MO) or with different types of migraine with aura (MA), including sporadic hemiplegic, familial hemiplegic, and probable familial hemiplegic, were screened for mutations in the four genes previously linked with different types of migraine ( ATP1A2 , CACNA1A , SCN1A , and KCNK18 ). Results Two missense mutations were found. One novel mutation in SCN1A , encoding α subunit of sodium channel, causing amino acid change M1500V localized to a region encoding inactivation loop between transmembrane domains III and IV of the channel, was detected in a female FHM patient. The M1500V mutation was absent in a group of 62 controls, as well as in the ExAC database. The second, already known missense mutation S231P in KCNK18 was found in a female MA patient. Additionally, a novel intronic polymorphism possibly affecting alternative splicing of SCN1A , at chr2:16685249, g.77659T>C, and c.4581+32A>G, located between exons 24 and 25, in a region encoding the inactivation loop of the sodium channel was found in a female MO patient. No mutations in ATP1A2 or CACNA1A were found in the study group. Conclusions The presence of SCN1A mutations and absence of mutations in ATP1A2 or CACNA1A suggest that the Polish patients represent FHM type 3. On the other hand, the presence of KCNK18 mutation indicated another FHM subtype. It could be speculated that contrary to other European populations, the genetic basis of migraine in the Polish population involves mutations in genes not included in the study. Next-generation sequencing methods should be implemented to identify other migraine-associated variants.
机译：背景与目的偏头痛是最常见的神经系统疾病，由环境和遗传因素共同引起，影响全世界约12％的成年人口。在家族性偏瘫偏头痛（FHM）家族中已鉴定出三个致病基因：CACNA1A，ATP1A2和SCNA1A。最近，还发现了KCNK18中的几种突变是偏头痛发生的病因。我们研究的目的是确定波兰人群中偏头痛的遗传背景。材料和方法筛选了60例无先兆偏头痛（MO）或不同类型的先兆偏头痛（MA）的患者，包括偶发性偏瘫，家族性偏瘫和可能的家族性偏瘫，这些患者先前与四个不同类型的偏头痛相关的基因突变偏头痛（ATP1A2，CACNA1A，SCN1A和KCNK18）。结果发现了两个错义突变。在女性FHM患者中检测到SCN1A中的一种新突变，该突变编码钠通道的α亚基，导致氨基酸变化M1500V定位于通道的跨膜结构域III和IV之间的失活环编码区域。在一组62个对照以及ExAC数据库中没有M1500V突变。在女性MA患者中发现了KCNK18中第二个已知的错义突变S231P。此外，一种新的内含子多态性可能影响SCN1A的选择性剪接，位于chr2：16685249，g.77659T> C和c.4581 + 32A> G，位于外显子24和25之间，位于编码钠灭活环的区域在一名女性MO患者中发现了该通道。在研究组中未发现ATP1A2或CACNA1A突变。结论SCN1A突变的存在以及ATP1A2或CACNA1A突变的缺失表明波兰患者代表FHM 3型。另一方面，KCNK18突变的存在表明另一种FHM亚型。可以推测，与其他欧洲人群相反，波兰人群中偏头痛的遗传基础涉及该研究未包括的基因突变。应当采用下一代测序方法来鉴定其他偏头痛相关变体。

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