Two novel SCNIA mutations identified in families with familial hemiplegic migraine

被引:20
作者
Weller, Claudia M. [1 ]
Pelzer, Nadine [2 ]
de Vries, Boukje [1 ]
Artigas Lopez, Merce [3 ]
De Fabregues, Oriol [4 ]
Pascual, Julio [5 ]
Ramos Arroyo, Maria A. [3 ]
Koelewijn, Stephany C. [1 ]
Stam, Anine H. [2 ]
Haan, Joost [2 ,6 ]
Ferrari, Michel D. [2 ]
Terwindt, Gisela M. [2 ]
van den Maagdenberg, Arn M. J. M. [1 ,2 ]
机构
[1] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RC Leiden, Netherlands
[2] Leiden Univ, Dept Neurol, Med Ctr, NL-2300 RC Leiden, Netherlands
[3] Complejo Hosp Navarra, Dept Med Genet, Navarra, Spain
[4] Univ Hosp Vall dHebron, Dept Neurol, Barcelona, Spain
[5] Univ Hosp Cent Asturias, Dept Neurol, Asturias, Spain
[6] Rijnland Hosp, Dept Neurol, Leiderdorp, Netherlands
关键词
Migraine; ion channel defects; familial hemiplegic migraine; SCNIA gene; PAROXYSMAL KINESIGENIC DYSKINESIA; SEVERE MYOCLONIC EPILEPSY; SODIUM-CHANNEL SCN1A; PRRT2; MUTATIONS; EPISODIC ATAXIA; GENE-MUTATIONS; INACTIVATION;
D O I
10.1177/0333102414529195
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background Familial hemiplegic migraine (FHM) is a rare monogenic subtype of migraine with aura, characterized by motor auras. The majority of FHM families have mutations in the CACNA1A and ATP1A2 genes; less than 5% of FHM families are explained by mutations in the SCN1A gene. Here we screened two Spanish FHM families for mutations in the FHM genes. Methods We assessed the clinical features of both FHM families and performed direct sequencing of all coding exons (and adjacent sequences) of the CACNA1A, ATP1A2, PRRT2 and SCN1A genes. Results FHM patients in both families had pure hemiplegic migraine with highly variable severity and frequency of attacks. We identified a novel SCN1A missense mutation p.Ile1498Met in all three tested hemiplegic migraine patients of one family. In the other family, novel SCN1A missense mutation p.Phe1661Leu was identified in six out of eight tested hemiplegic migraine patients. Both mutations affect amino acid residues that either reside in an important functional domain (in the case of Ile(1498)) or are known to be important for kinetic properties of the Na(V)1.1 channel (in the case of Phe(1661)). Conclusions We identified two mutations in families with FHM. SCN1A mutations are an infrequent but important cause of FHM. Genetic testing is indicated in families when no mutations are found in other FHM genes.
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收藏
页码:1062 / 1069
页数:8
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