|Number||Exon/Intron||Nucleotide change||Protein change||Location||Mutation type||Consequences||Phenotype||Inheritance||Reference|
|1464||26||c.4946T>A||p.Leu1649Gln||DIVS4||Missense||N→P/O (113); LOF||FHM||Familial(Paternal,FHM), p=6/6||Vanmolkot KR.2007|
|Number||Nucleotide change||Protein change||Location||Phenotype||Functional defect type||Details of the major biophysical abnormalities.||Reference|
|39||c.4946T>A||p.Leu1649Gln(L1649Q)||DIVS4||FHM||LOF||Failed to generate measurable whole-cell current.||Kahlig KM.2008|
|Number||Nucleotide change||Protein change||Mutation type||Proband's phenotype||1st transmitter's phenotype||Mosaic||Affected generations||Penetrance||Reference|
|[c.4946T>A] Clinical description|
Mutation scanning of the SCN1A gene in the probands of the 10 families revealed one mutation in a North American family of Caucasian descent. The proband (III-4), aged 51 years, has hemiplegic migraine attacks since the age of 10 with a frequency that varies from twice a month to once a year. The attacks always start with blurred vision with dark spots, followed within minutes by spreading hemiparasthesia and hemiparesis with dysarthria and dysphasia. After 20-30 minutes, this is followed by a hemicranial throbbing headache, which is always located on the side opposite to the hemiparesis and is accompanied by nausea, vomiting, photo- and phonopobia. Six additional family members suffer from typicial hemiplegic migraine attacks as well, with an age of onset varying from 11 to 24 years. The authors classified individual IV-3 also as affected, despite the fact that he only has had one attack of FHM so far. Authors feel that because of his young age (22) subsequent attacks are still likely to occur. Besides hemiplegic attacks, individual III-2 suffers from migraine with and without aura and individual IV-3 suffers from migraine without aura. No cerebellar signs or epilepsy symptoms were reported in this family(Vanmolkot KR, et al. Hum Mutat. 2007 May;28(5):522. ).
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Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China
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