Variable neurologic phenotype in a GEFS+ family with a novel mutation in SCN1A Krista Mahoney, Susan J. Moore, David Buckley, Muhammed Alam, Patrick Parfrey,

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Variable neurologic phenotype in a GEFS+ family with a novel mutation in SCN1A Krista Mahoney, Susan J. Moore, David Buckley, Muhammed Alam, Patrick Parfrey, Sharon Penney, Nancy Merner, Kathy Hodgkinson, Terry-Lynn Young Seizure - European Journal of Epilepsy Volume 18, Issue 7, Pages 492-497 (September 2009) DOI: 10.1016/j.seizure.2009.04.009 Copyright © 2009 Terms and Conditions

Fig. 1 Core pedigree of Newfoundland family showing both typical and novel features of GEFS+ associated with the epilepsy-associated haplotype (red) on chromosome 2q24 in the vicinity of SCN1A. Markers are listed on the left and alleles given in size (base pairs) or specific nucleotide. The proband is indicated by an arrow. Gender has been masked using diamond symbols to protect confidentiality. Seizure - European Journal of Epilepsy 2009 18, 492-497DOI: (10.1016/j.seizure.2009.04.009) Copyright © 2009 Terms and Conditions

Fig. 2 Sequencing traces (forward direction) showing the heterozygous c.1162 T>C transition in exon 8 of SCN1A of the proband's (IV:1, Fig. 1) genomic DNA. The amino acid translations (top) show the Y388H amino acid substitution. Seizure - European Journal of Epilepsy 2009 18, 492-497DOI: (10.1016/j.seizure.2009.04.009) Copyright © 2009 Terms and Conditions

Fig. 3 Conservation of SCN1A in the vicinity of Y388 and location of Y388H within the SCN1A protein. (A) Weblogo was used to align orthologs from Homo sapiens (NP_008851), Pan troglodytes (XP_515872), Mus musculus (NP_061203), Rattus norvegicus (NP_110502), Danio rerio (NP_956426), Drosophila melanogaster (NP_001036280), and Nasonia vitripennis (NP_001128389). The tyrosine (Y) residue at position 388 of the SCN1A protein compared to other sodium channel proteins is marked by a red arrow. (B) Y388H (red triangle) results in the substitution of a neutral polar tyrosine residue to a polar basic histidine in the loop between the S5 and S6 segments of domain 1 of the SCN1A protein. Segments 5 and 6 (darker blue) form the ion channel pore and segment 4 is the voltage sensor. Seizure - European Journal of Epilepsy 2009 18, 492-497DOI: (10.1016/j.seizure.2009.04.009) Copyright © 2009 Terms and Conditions