SMEI (716) 27 SMEB (99) 1 6 2 GEFS+ (43) Supplementary Figure S1: Venn diagram shows intersection (i.e., number of common mutations) between SMEI, SMEB, and/or GEFS+ as indicated.
Missense Nonsense Small deletion Large deletion Small duplication Large duplication In-del Splice site Supplementary Figure S2: Pie chart displaying various types of mutations (in percentage) known in SCN1A gene to be associated with DS. For details see Supplementary Table S1.
epilepsy 100 90 Per rcent affecte ed with a giv ven type of 80 70 60 50 40 30 20 10 0 All Population Caucasian Asian Arabic SMEI SMEB GEFS+ Supplementary Figure S3: Bar diagram depicting relative frequency (percent) of patients exhibiting SMEI, SMEB or GEFS+ phenotype in the three different ethnic groups. For details of mutations and number of cases, see Supplementary Table S1
Supplementary Figure S4: Phylogenetic conservation of residues affected by the missense mutations in SCN1A protein as revealed by the multiple sequence alignment [Homo sapiens, H.s (GenBank: NP_001159436.1), Mus musculus, M.m (NP_061203.2); Rattus norvegicus, R.n (AAA79965.1); Bos taurus, B.t (NP_001180147.1); Canis lupus familiaris, C.l (XP_535941.2); Equus caballus, E.c (XP_001916728.2) H W Mutation T N V F T P DN C ST P Q GVI R I S N D H.s. MEQT...KDDDENGPKPNSDLEAGKNLPFIYGDIPPEMVSEPLEDLDPYYINKK-TFIVLNKGKAIFRFSATSALYILTPFNPLRKIAIKILVHSLF...YTF M.m. MEQT...KDDDENGPKPNSDLEAGKNLPFIYGDIPPEMVSEPLEDLDPYYINKK-TFIVLNKGKAIFRFSATSALYILTPFNPLRKIAIKILVHSLF...YTFYTF R.n. MEQT...KDDDENGPKPNSDLEAGKNLPFIYGDIPPEMVSEPLEDLDPYYINKK-TFIVLNKGKAIFRFSATSALYILTPFNPLRKIAIKILVHSLF...YTF B.t. MEQT...KDDDEHGPKPNSDLEAGKNLPFIYGDVPPEMVSEPLEDLDPYYINKK-TFIVLNKGKAIFRFSATSALYILTPFNPLRKIAIKILVHSLF...YTF C.l. MEQT...KDDDENGPKPNSDLEAGKNLPFIYGDIPPEMVSEPLEDLDPYYINKK-TFIVLNKGKAIFRFSATSALYILTPFNPLRKIAIKILVHSLF...YTF E.c. MEQT...KDDDENGPKPNSDLEAGKNLPFIYGDIPPEMVSEXLEDLDPYYINKKXTFIVLNKGKAIFRFSATSALYILTPFNPLRKIAIKILVHSLF...YTF 1 45 58 61 68 74 78 79 84 90 91 98 101 103 104 105 R R V E K G MT V M Mutation PE K T RSR V RY N R A KL E KS SR T Y N I R H.s. TGIYTFESLIKIIARGFCLEDFTFLRDPWNWLDFTVITFAYVTEFVDLGNVSALRTFRVLRALKTISVIPGLKTIVGALIQSVKKLSDVMILTVFCLSVFALI M.m. TGIYTFESLIKIIARGFCLEDFTFLRDPWNWLDFTVITFAYVTEFVDLGNVSALRTFRVLRALKTISVIPGLKTIVGALIQSVKKLSDVMILTVFCLSVFALI R.n. TGIYTFESLIKIIARGFCLEDFTFLRDPWNWLDFTVITFAYVTEFVDLGNVSALRTFRVLRALKTISVIPGLKTIVGALIQSVKKLSDVMILTVFCLSVFALI B.t. TGIYTFESLIKIIARGFCLEDFTFLRDPWNWLDFTVITFAYVTEFVDLGNVSALRTFRVLRALKTISVIPGLKTIVGALIQSVKKLSDVMILTVFCLSVFALI C.l. TGIYTFESLIKIIARGFCLEDFTFLRDPWNWLDFTVITFAYVTEFVDLGNVSALRTFRVLRALKTISVIPGLKTIVGALIQSVKKLSDVMILTVFCLSVFALI E.c. TGIYTFESLIKIIARGFCLEDFTFLRDPWNWLDFTVITFAYVTEFVDLGNVSALRTFRVLRALKTISVIPGLKTIVGALIQSVKKLSDVMILTVFCLSVFALI 162 163 171 175 177 178 179 188 190 191 194 199 212 217 218 223 226 227 232 233 108 112 239 243 118 124 127 252 254 259 A CL P Mutation W R RS RG I R I F VE R W DGITS R E H.s. GLQLFMGNLRNKCIQWPPTNASLEEHSIEKNITVNYNGTLINETVFEFDWKSYIQDSRYHYFLEGFLDALLCGNSSDAGQCPEGYMCVKAGRNPNYGYTSFDT M.m. GLQLFMGNLRNKCVQWPPTNASLEEHSIEKNITMDYNGTLVNETVFEFDWKSYIQDSRYHYFLEGVLDALLCGNSSDAGQCPEGYMCVKAGRNPNYGYTSFDT R.n. GLQLFMGNLRNKCVQWPPTNASLEEHSIEKNVTTDYNGTLVNETVFEFDWKSYIQDSRYHYFLEGVLDALLCGNSSDAGQCPEGYMCVKAGRNPNYGYTSFDT B.t. GLQLFMGNLRNKCVQWPPTNASLEEHTVEKNITKNYNGTFVNETRNEFDWKSYIQDSRYHYFLEGFSDALLCGNSSDAGQCPEGYMCVKAGRNPNYGYTSFDT C.l. GLQLFMGNLRNKCVQWPPTNASLEEHSIERNITVNYNGTLVNETLIEFDWKSYIQDSRYHYFLEGILDALLCGNSSDAGQCPEGYMCVKAGRNPNYGYTSFDT E.c. GLQLFMGNLRNKCVQWPPTNASLEEHSIEKNVTVNYNGTLVNETLIEFDWKSYIQDSRYHYFLEGFLDALLCGNSSDAGQCPEGYMCVKAGRNPNYGYTSFDT 265 277 280 281 290 291 297 314 322 340 342 343 345 351 355 356 357 358 359 363 366 Supplementary Figure S4 ccontinued in next page
H Q S L E C Mutation LQ NDRG H C P V V F W IN M N Q G G H.s. FSWAFLSLFRLMTQDFWENLYQLTLRAAGKTYMIFFVLVIFLGSFYLINLILAVVAMAYEEQ...EGNRLTY...SQTSRSS...VIIDKPATDDNGTT...HEGNRLTY SQTSRSS VIIDKPATDDNGTT M.m. FSWAFLSLFRLMTQDFWENLYQLTLRAAGKTYMIFFVLVIFLGSFYLINLILAVVAMAYEEQ...EGNRLTY...SQTSRSS...-----------GTT...H R.n. FSWAFLSLFRLMTQDFWENLYQLTLRAAGKTYMIFFVLVIFLGSFYLINLILAVVAMAYEEQ...EGNRLTY...SQTSRSS...VIIDKPATDDNGTT...H B.t. FSWAFLSLFRLMTQDFWENLYQLTLRAAGKTYMIFFVLVIFLGSFYLINLILAVVAMAYEEQ...EGNRLTY...SQTSRSS...-----------GTT...H C.l. FSWAFLSLFRLMTQDFWENLYQLTLRAAGKTYMIFFVLVIFLGSFYLINLILAVVAMAYEEQ...EGNRLTY...SQTSRSS...-----------GTT...H E.c. FSWAFLSLFRLMTQDFWENLYQLTLRAAGKTYMIFFVLVIFLGSFYLINLILAVVAMAYEEQ...EGNRLTY...SQTSRSS...VIIDKPATDDNGTT...H 377 7 378 382 383 3 384 385 388 8 393 3 395 400 0 403 406 409 412 413 422 2 426 542 626 6 674 Mutation D P T K C M R I RR K C Q H.s. VVNLVVMDPFVDLAITICIVLNTLFMAMEHYPMTDHFNNVLTVGNLVFTGIFTAEMFLKIIAMDPYYYFQEGWNIFDGFIVTLSLVELGLANVEGLSVLRSFR M.m. IVNLVVMDPFVDLAITICIVLNTLFMAMEHYPMTEHFNHVLTVGNLVFTGIFTAEMFLKIIAMDPYYYFQEGWNIFDGFIVTLSLVELGLANVEGLSVLRSFR R.n. IVNLVVMDPFVDLAITICIVLNTLFMAMEHYPMTEHFNHVLTVGNLVFTGIFTAEMFLKIIAMDPYYYFQEGWNIFDGFIVTLSLVELGLANVEGLSVLRSFR B.t. VVNLVVMDPFVDLAITICIVLNTLFMAMEHYPMTDHFNNVLTVGNLVFTGIFTAEMFLKIIAMDPYYYFQEGWNIFDGFIVTLSLVELGLANVEGLSVLRSFR C.l. IVNLVVMDPFVDLAITICIVLNTLFMAMEHYPMTEHFNNVLTVGNLVFTGIFTAEMFLKIIAMDPYYYFQEGWNIFDGFIVTLSLVELGLANVEGLSVLRSFR E.c. IVNLVVMDPFVDLAITICIVLNTLFMAMEHYPMTEHFNNVLTVGNLVFTGIFTAEMFLKIIAMDPYYYFQEGWNIFDGFIVTLSLVELGLANVEGLSVLRSFR 76 62 78 83 78 85 78 88 79 90 79 93 80 08 F Q M I H P A C SE T Mutation K F L T C F CCPIH YF PDELH YR G K KL RV H.s. LLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKDCVCKIASDCQLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCMEVAGQ M.m. LLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKDCVCKIATDCKLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCMEVAGQ R.n. LLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKDCVCKIATDCKLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCMEVAGQ B.t. LLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKDCVCKINSECKLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCMEVAGQ C.l. LLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKDCVCKISTSCELPRWHMNDFFHSFLIVFRVLCGEWIETMWDCMEVAGQ E.c. LLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKDCVCKIASDCQLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCMEVAGQ 875 890 896 899 902 81 12 927 931 932 933 934 935 84 42 84 43 939 940 942 943 944 945 946 85 53 949 950 952 954 956 957 959 960 85 59 86 62 K V P Mutation V I R LA IF F R G E K H.s. AMCLTVFMMVMVIGNLVVLNLFLALLLSSFSADNLAATDDDNEMNNLQIAVDRMHKGVAYVKRKIYEFIQQSFIRKQKILDEIKPLDDLNNKKDSCMSNHTAE M.m. AMCLTVFMMVMVIGNLVVLNLFLALLLSSFSADNLAATDDDNEMNNLQIAVDRMHKGIAYVKRKIYEFIQQSFVKKQKILDEIKPLDDLNNRKDNCISNHTTE R.n. AMCLTVFMMVMVIRNLVVLNLFLALLLSSFSADNLAATDDDNEMNNLQIAVDRMHKGVAYVKRKIYEFIQQSFVRKQKILDEIKPLDDLNNRKDNCTSNHTTE B.t. AMCLTVFMMVMVIGNLVVLNLFLALLLSSFSADNLAATDDDNEMNNLQIAVDRMHKGIAYVKRKIYEFIQQSFVRKQKILDEIKPLDDLNNRKDNCMSNHTTE C.l. AMCLTVFMMVMVIGNLVVLNLFLALLLSSFSADNLAATDDDNEMNNLQIAVDRMHKGVAYVKRKIYEFIQQSFVRKQKILDEIKPLDDLNNKKDSCMSNHTTE E.c. AMCLTVFMMVMVIGNLVVLNLFLALLLSSFSADNLAATDDDNEMNNLQIAVDRMHKGIAYVKRKIYEFIQQSFVRKQKILDEIKPLDDLNNKKDNCMSNHTAE 973 976 979 982 983 985 986 990 993 998 1006 1068 Supplementary Figure S4 ccontinued in next page
S R G Mutation R PK K QR K FT R DY Q NM CD P L PA T NV S PN H.s. IGKDLDYLK...GKQWWNLRRTCFRIVEHNWFETFIVFMILLSSGALAFEDIYIDQRKTIKTMLEYADKVFTYIFILEMLLKWVAYGYQTYFTNAWCWLDFLI M.m. IGKDLDCLK...GKQWWNLRRTCFRIVEHNWFETFIVFMILLSSGALAFEDIYIDQRKTIKTMLEYADKVFTYIFILEMLLKWVAYGYQTYFTNAWCWLDFLI R.n. IGKDLDCLK...GKQWWNLRRTCFRIVEHNWFETFIVFMILLSSGALAFEDIYIDQRKTIKTMLEYADKVFTYIFILEMLLKWVAYGYQTYFTNAWCWLDFLI B.t. IGKDLDYLK...GKQWWNLRRTCFRIVEHNWFETFIVFMILLSSGALAFEDIYIDQRKTIKTMLEYADKVFTYIFILEMLLKWVAYGYQTYFTNAWCWLDFLI C.l. IGKDLDYLK...GKQWWNLRRTCFRIVEHNWFETFIVFMILLSSGALAFEDIYIDQRKTIKTMLEYADKVFTYIFILEMLLKWVAYGYQTYFTNAWCWLDFLI E.c. IGKDLDYLK...GKQWWNLRRTCFRIVEHNWFETFIVFMILLSSGALAFEDIYIDQRKTIKTMLEYADKVFTYIFILEMLLKWVAYGYQTYFTNAWCWLDFLI 1204 1207 1208 1210 1213 1214 1221 1230 1231 1233 G D S V T Mutation DF S V TP P M V M G L R IK P R H V MS PI H.s. VDVSLVSLTANALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALLGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYHCINTTTGDRFDIEDVNNHT M.m. VDVSLVSLTANALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALLGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYHCVNTTTGDIFEISEVNNHS R.n. VDVSLVSLTANALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALLGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYHCVNTTTGDTFEITEVNNHS B.t. VDVSLVSLTANALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALLGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYHCVNTTTGDMFDISEVNNHS C.l. VDVSLVSLTANALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALLGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYHCINTTTGDMFDITEVNNHS E.c. VDVSLVSLTANALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALLGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYHCINTTTGDRFEIEEVNNHS 1308 1309 1316 1320 1325 1326 1328 1335 1339 Y D E RL C Mutation G Y GSG CF RP D I VR M P LS K IHS W S SK V MGY H G H.s. DCLKLIERNETARWKNVKVNFDNVGFGYLSLLQVATFKGWMDIMYAAVDSRNVELQPKYEESLYMYLYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQD M.m. DCLKLIERNETARWKNVKVNFDNVGFGYLSLLQVATFKGWMDIMYAAVDSRNVELQPKYEESLYMYLYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQD R.n. DCLKLIERNETARWKNVKVNFDNVGFGYLSLLQVATFKGWMDIMYAAVDSRNVELQPKYEESLYMYLYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQD B.t. DCLILIERNETARWKNVKVNFDNVGFGYLSLLQVATFKGWMDIMYAAVDSRNVELQPKYEESLYMYLYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQD C.l. DCLKLIERNETARWKNVKVNFDNVGFGYLSLLQVATFKGWMDIMYAAVDSRNVELQPKYEESLYMYLYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQD E.c. DCLKLIERNETARWKNVKVNFDNVGFGYLSLLQVATFKGWMDIMYAAVDSRNVELQPKYEESLYMYLYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQD 1396 1414 4 1416 1417 1418 1422 2 1423 1426 1427 1429 1431 1 1433 3 1434 4 1437 1441 1 1238 1239 1344 1245 1450 1451 1 1350 1249 1250 1454 4 1353 1254 1255 1358 1461 1 1462 1463 1260 1263 1265 1266 1366 1367 1370 1470 1472 1270 1475 1476 1274 1275 1376 1378 1480 1483 1484 4 1485 1385 1284 1489 1287 1288 1390 1391 1393 1394 1497 L Mutation L K K T IP SAV R K C E E R P C H.s. IFMTEEQKKYYNAMKKLGSKKPQKPIPRPGNKFQGMVFDFVTRQVFDISIMILICLNMVTMMVETDDQSEYVTTILSRINLVFIVLFTGECVLKLISLRHYYF M.m. IFMTEEQKKYYNAMKKLGSKKPQKPIPRPGNKFQGMVFDFVTRQVFDISIMILICLNMVTMMVETDDQSDYVTSILSRINLVFIVLFTGECVLKLISLRHYYF R.n. IFMTEEQKKYYNAMKKLGSKKPQKPIPRPGNKFQGMVFDFVTRQVFDISIMILICLNMVTMMVETDDQSDYVTSILSRINLVFIVLFTGECVLKLISLRHYYF B.t. IFMTEEQKKYYNAMKKLGSKKPQKPIPRPGNKFQGMVFDFVTRQVFDISIMILICLNMVTMMVETDDQSDCVTSILSRINLVFIVLFTGECVLKLISLRHYYF C.l. IFMTEEQKKYYNAMKKLGSKKPQKPIPRPGNKFQGMVFDFVTRQVFDISIMILICLNMVTMMVETDDQSEYVTNILSRINLVFIVLFTGECVLKLISLRHYYF E.c. IFMTEEQKKYYNAMKKLGSKKPQKPIPRPGNKFQGMVFDFVTRQVFDISIMILICLNMVTMMVETDDQSEYVTNILSRINLVFIVLFTGECVLKLISLRHYYF 149 99 150 03 151 11 152 23 153 38 153 39 154 43 154 44 154 45 155 55 156 61 157 75 157 79 158 86 158 88 Supplementary Figure S4 ccontinued in next page 159 92 159 96
S G M N H HM L TC Mutation S Y FI T V L S QETG S Q C E MCR PSV K PA ITRR F SFDD SW S C H.s. TIGWNIFDFVVVILSIVGMFLAELIEKYFVSPTLFRVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGMSNFAYVKREVGIDD M.m. TIGWNIFDFVVVILSIVGMFLAELIEKYFVSPTLFRVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGMSNFAYVKREVGIDD R.n. TIGWNIFDFVVVILSIVGMFLAELIEKYFVSPTLFRVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGMSNFAYVKREVGIDD B.t. TIGWNIFDFVVVILSIVGMFLAELIEKYFVSPTLFRVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGMSNFAYVKREVGIDD C.l. TIGWNIFDFVVVILSIVGMFLAELIEKYFVSPTLFRVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGMSNFAYVKREVGIDD E.c. TIGWNIFDFVVVILSIVGMFLAELIEKYFVSPTLFRVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGMSNFAYVKREVGIDD 1605 1608 1611 1612 1616 1619 1630 1632 1636 1637 1638 1639 1642 1645 1648 1653 1656 1657 1658 1660 1661 1662 1664 1667 1668 1672 1673 1674 1675 1677 1682 1683 1684 1685 1687 1688 T R NF CMV Mutation V I NK R R PCR L RG E R G EN HFN F THST KK T K H.s. MFNFETFGNSMICLFQITTSAGWDGLLAPILNSKPPDCDPNKVNPGSSVKGDCGNPSVGIFFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPLSEDDFE M.m. MFNFETFGNSMICLFQITTSAGWDGLLAPILNSKPPDCDPNKVNPGSSVKGDCGNPSVGIFFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPLSEDDFE R.n. MFNFETFGNSMICLFQITTSAGWDGLLAPILNSKPPDCDPNKVNPGSSVKGDCGNPSVGIFFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPLSEDDFE B.t. MFNFETFGNSMICLFQITTSAGWDGLLAPILNSKPPDCDPNKVNPGSSVKGDCGNPSVGIFFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPLSEDDFE C.l. MFNFETFGNSMICLFQITTSAGWDGLLAPILNSKPPDCDPNKVNPGSSVKGDCGNPSVGIFFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPLSEDDFE E.c. MFNFETFGNSMICLFQITTSAGWDGLLAPILNSKPPDCDPNKVNPGSSVKGDCGNPSVGIFFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPLSEDDFE 1707 1709 1713 1714 1716 1721 1724 1725 1726 1739 1741 1742 1749 1754 1756 1762 1763 1769 1770 1771 1773 1780 1781 1782 1783 L S K D Mutation I G SP F T LTL W YT EK I H.s. MFYEVWEKFDPDATQFMEFEKLSQFAAALEPPLNLPQPNKLQLIAMDLPMVSGDRIHCLDILFAFTKRVLGESGEMDALRIQMEERFMASNPSKVSYQPITTT M.m. MFYEVWEKFDPDATQFMEFEKLSQFAAALEPPLNLPQPNKLQLIAMDLPMVSGDRIHCLDILFAFTKRVLGESGEMDALRIQMEERFMASNPSKVSYQPITTT R.n. MFYEVWEKFDPDATQFMEFEKLSQFAAALEPPLNLPQPNKLQLIAMDLPMVSGDRIHCLDILFAFTKRVLGESGEMDALRIQMEERFMASNPSKVSYQPITTT B.t. MFYEVWEKFDPDATQFMEFEKLSQFAAALEPPLNLPQPNKLQLIAMDLPMVSGDRIHCLDILFAFTKRVLGESGEMDALRIQMEERFMASNPSKVSYQPITTT C.l. MFYEVWEKFDPDATQFMEFEKLSQFAAALEPPLNLPQPNKLQLIAMDLPMVSGDRIHCLDILFAFTKRVLGESGEMDALRIQMEERFMASNPSKVSYQPITTT E.c. MFYEVWEKFDPDATQFMEFEKLSQFAAALEPPLNLPQPNKLQLIAMDLPMVSGDRIHCLDILFAFTKRVLGESGEMDALRIQMEERFMASNPSKVSYQPITTTF W L Q Q M PMVSG R DI G SGE Q S S S Q T 1808 1812 1831 1832 1835 1852 1855 1856 1857 1861 1866 1867 1880 1881 1787 1788 1792 1692 1694 1795 1909 Mutation T G G H.s. LKRKQEEVSAVIIQRAYRRHLLKRTVKQASFTYNKNKIKGGANLLIKEDMI M.m. LKRKQEEVSAVIIQRAYRRHLLKRTVKQASFTYNKNKLKGGANLLVKEDML R.n. LKRKQEEVSAVIIQRAYRRHLLKRTVKQASFTYNKNKLKGGANLLVKEDMI B.t. LKRKQEEVSAVIIQRAYRRHLLKRTVKQASFTYNKNKIKGGANLLVKEDMI C.l. LKRKQEEVSAVIIQRAYRRHLLKRTVKQASFTYNKNKIKGGANLLVKEDMI E.c. LKRKQEEVSAVIIQRAYRRHLLKRTVKQASFTYNKNKIKGGANLLVKEDMI 1922 1928 1957
100 90 80 Percent mu utations 70 60 Missense 50 Truncation Large deletion 40 Large duplication 30 Splice site 20 10 0 SMEI SMEB GEFS+ Supplementary Figure S5: Bar diagram showing relative frequency (percent) of different types of mutations known in SCN1A to be causing SMEI, SMEB or GEFS+ phenotype. Here, truncation mutation refers to both frame shift and nonsense mutations. For details of mutations and number of cases, see Supplementary Table S1.
ercent muta ations P 100 90 80 70 60 50 40 30 20 10 De novo Inherited 0 SMEI SMEB GEFS+ Supplementary Figure S6: Bar diagram showing the relative levels (percentage) of de novo and inherited mutations in patients with SMEI, SMEB or GEFS+ phenotype, as indicated. For details of mutations and number of cases, see Supplementary Table S1.