Amyotrophic Lateral Sclerosis 11

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

C9orf72, SOD1, PON1, ATXN2, FUS, TARDBP, TAF15, OPTN, SQSTM1, MATR3, TBK1, UNC13A, CHMP2B, NEK1, DAO, CFAP410, DCTN1, SIGMAR1, TREM2, CHCHD10, ANG, NEFH, UBQLN2, EPHA4, PFN1, HNRNPA1, VCP, VAPB, PRPH, SETX, HNRNPA2B1, PPARGC1A, DPP6, CCNF, ANXA11, GLT8D1, ERBB4, GLE1, FIG4, SCFD1, SLC1A2, EWSR1, PON2, PON3, GFAP, MOBP, TP53, ARHGEF28, PTGS2, SOD2, GSR, TNFRSF21, SLC6A1, CD40LG, PLA2G4A, CAMK1G, DBR1, GSTP1, ADARB1, CASP3, AQP4, C5AR1, C3, NEFM, KCNJ10, BCL2L1, ZNF106, KIF1B, MSTN, CASP9, PSMC4, PTPRZ1, RARA, EPG5, ALS2, CASP12, MAPT, IGF1R, IGF2R, TUBA4A, KIFAP3, KIF5A, TRPM7, SARM1, ATXN3, SPG11, PSEN1, TNIP1, SUSD2, MOB3B, DCDC2, HFE, CENPV, SUN3, CST3, DCTN4, ST3GAL3, GTF2H1, ICE1, GRN, CSF2, SUN2, GRIA2, CPNE4, LAMA3, LAMC2, PTBP1, STMN1, NUP62, STK36, MAK16, NUP98, NEFL, GABPA, SRRM2, RBMS3, NFE2L2, GRIP1, GDNF, ARAP2, APTX, SCN8A, NPEPPS, APP, KIAA0513, SMN1, ARHGEF2, WASHC5, SNURF, APOE, TIAM1, AR, NRXN1, TNF, IGFALS, KHDRBS1, IGF1, PNO1, VEGFA, BDNF, ACTB, BCL2, SNCA, SMN2, NME9, GTPBP1, CNTF, KIAA0040, PIGL, SNRPN, ADA, SIRT1, CCL2, GRM2, IL6, MAPK1, TIA1, CDK5, P2RX7, CHI3L1, GPNMB, RIPK1, MIR206, CHGB, CHIT1, P4HB, GRM5, PARP1, IL1B, HTT, TNFRSF1B, EPO, MIR338, LY6E, VGF, ABCB1, MCIDAS, GRM1, DECR1, APEX1, CYBB, PINK1, ZNF512B, XBP1, HCLS1, ADIPOQ, HGF, MMP9, LMNB1, ATG5, NGF, NRG1, SIGLEC7, GRIA1, TANK, DNM1L, KHSRP, FGF2, SS18L1, CSF3, TUSC2, IL2RB, PSIP1, HSPB1, RBM45, TCF3, RAN, CUX1, RNF19A, MAPK14, NLRP3, SMUG1, SFPQ, CASP1, AIF1, ZNF569, KEAP1, TPPP, MST1, CHCHD2, RNASE4, RBM8A, RREB1, MSC, TMEM189-UBE2V1, OXR1, TMEM189, CHGA, ATXN2-AS, RRM2, CX3CR1, ZNF629, ATF6, TMED9, CNR2, ASPM, ZNF253, NAIP, ELP3, LGALS3, HRES1, PPARG, UBE2V1, FMR1, ERN1, EPHB2, LCN2, HNRNPA1P10, HSF1, TTR, ASPA, ASIP, SEMA3A, VDAC1, ZNF763, A1CF, TLR4, CAT, CCS, THY1, ZNF436, HSPA4, ROPN1L, NIPA1, EDN1, CDK5R1, TGM2, TNPO1, CASZ1, CXCL8, RTN4, LGALS1, RNASEL, TMEM106B, S100A6, SLC1A1, SOX2, STAT3, TFAM, TGFB1, SUMO1, AHSA1, SLC35A1, VRK1, CLEC10A, AIMP2, ELP1, HNRNPDL, VAPA, GRAP2, S100B, RRM1, VPS54, RNASE1, MSMB, FIS1, COX2, FOXP3, NOS1, NOS2, NTF3, P2RX4, HSPB8, PIN1, POLDIP2, PTPA, MAP2K5, PRNP, RAG2, IL4, GAL3ST1, CRK, AGER, HNRNPH2, ADAR, HNRNPC, CRP, EGFR, ADCYAP1, LMLN, MIR155, PRMT1, SUGP1, ANPEP, HNRNPH1, MTOR, CST12P, FXN, C19orf12, PDIA3, CTNNB1, GAPDH, TMPRSS13, CYP27A1, HIF1A, CS, LRRK2, IFNG, ALAD, DES, CP, CCL27, FCGR3A, PPIA, PHGDH, SLC52A3, FCGR3B, CFDP1, NEAT1, SPAG11B, ATRNL1, SLC30A3, ATM, PRRT2, SYT1, FMO1, CST7, GAP43, PDLIM3, GSTK1, SIRT2, XIAP, DENR, CAV1, SLPI, CAST, TFEB, FN1, CCR2, PRKN, APRT, STMN2, TLR2, TFPI2, ATHS, PDC, MAPK8, CREBBP, UCHL1, MOK, NOP56, SLCO6A1, RANBP2, ATG7, DNMT1, RASGRF1, UCP2, RELA, TSPO, PRKCA, TXN, CTBS, SIRT3, RRAD, TTN, CTF1, ATP13A2, TRPM2, ATXN1, RAB5A, DAPK2, PVALB, UTRN, PRKCB, XBP1P1, FBXO32, SPAG11A, BECN1, RAB3GAP2, WNT5A, EPHA3, EPHA1, VSNL1, CRMP1, VIM, EIF4G2, PSMD2, SGCG, VDR, PTGER2, TNFRSF1A, EGF, HPGDS, GARS1, TSHZ1, MAOB, SNPH, HDAC4, SRR, NAT10, SPAST, LIG4, LRP4, MIR146A, HMOX1, HMGB1, LSM2, MAP2, SIL1, GORASP1, PDIA2, MTHFSD, NPY, ERVK-12, SOX9, ERVK-2, LEP, ERVK-11, MFAP1, MTCO2P12, GJD2, IL10, RIPK3, DDX20, ABL1, SLC17A6, STAT5A, PCYT1B, IGF2, CTR9, FGGY, TDP1, CCDC88A, HDAC9, ABCG2, MFN1, KDR, TEAD1, RHOT1, DNAJB2, MET, ERVK-22, KITLG, CHAF1A, LINC01672, CHI3L2, UBQLN1, MALAT1, FNDC3A, GLS, PADI1, ASRGL1, NRP1, CLU, GH1, SNAP25, RAB11A, DBNL, NFKB1, ALYREF, MIR1825, CCN2, NOTCH1, KCNIP3, HSP90B2P, PIK3R4, ARHGEF7, ALB, GEMIN4, ALPP, SOS1, HDAC6, ALS3, DERL1, WNK1, AKT1, GPX3, HDAC1, MTHFR, SLC25A37, AKT3, PNPLA6, LILRA2, MIR193A, RBBP9, PAPOLA, NES, YWHAQ, ARPP21, MIR29B1, MIR93, JTB, MIR29B2, MRPS30, MIR143, MIR23A, MIR15A, MIR183, ERGIC1, OGA, P2RX5-TAX1BP3, OLIG2, EBI3, NAMPT, MIR4299, PPIF, ABCC9, SH2B3, OCLN, FGFBP1, MFN2, MIR4649, CALCOCO2, PINK1-AS, LZTS3, ELDR, TPTEP2-CSNK1E, GDA, CREB5, H3P13, CCL4L2, PTGES, BAG3, GDF11, GLYAT, TSBP1, LOC643387, MIR17HG, MIR326, MIR375, ERLIN1, MIR378A, MIR494, MIR193B, MIR524, ZNF704, POU5F1P3, POU5F1P4, RAMP3, CARM1, UNC13B, MIR582, OLFM1, RACK1, TUBA1B, MIR638, LANCL1, STUB1, MIR1246, POTEF, CLEC4C, MIR142, NOP53, SRCIN1, RUBCNL, IFT74, UBN1, ATAT1, DHDDS, SLC40A1, FLVCR1, KCNIP1, ASAP1, GGNBP2, ASCC1, HDAC11, ATL1, ARHGAP24, REM1, MIR139, TTBK1, PABPC1, CYFIP2, NOX1, ATAD1, ANKRD1, CACYBP, AGO2, HTRA2, HCAR1, TUBGCP4, BTBD10, COQ2, POLDIP3, EIF3K, GEMIN6, MMP28, NMD3, NLN, FAM160B1, SLC30A6, MAGEE1, NGLY1, KCNT1, ZKSCAN7, PRMT8, APH1A, LXN, FAM20C, NUP107, SLC12A5, NDRG2, MCOLN1, SAGE1, HAMP, NGB, WDR41, RMDN3, MTPAP, COP1, WIPI1, XRN1, P2RY12, DCUN1D1, IL23A, SIRT6, BCL11B, IGF2-AS, ACD, CUEDC2, BSCL2, AATF, WNT3A, CAMTA1, HCA1, NUP205, ATG4B, MLC1, PLCB1, ALS2CL, MGRN1, TICAM1, BICD2, SPDYA, HNRNPA3, MED19, FLCN, SIRT5, WDTC1, MIF-AS1, TAAR6, MYH15, P2RX2, GADL1, TGM6, ERCC6L2, KMT5A, ATG14, CCL4L1, AAK1, MGLL, MIRLET7B, PDAP1, MIR126, PARK7, JPH3, TTBK2, FGF21, GLCE, GRIN3B, NT5C3B, CARD16, AZIN2, L3MBTL1, OSBPL3, EGLN3, SYT9, DNER, NOC2L, MTDH, MCU, SPAG8, ANKRD2, THEM4, PANX1, ZFYVE27, TFIP11, PPIL2, SLC7A11, PPP1R15A, TPH2, CD2AP, JDP2, PDSS1, DDX58, PPARGC1B, PADI4, TRIM69, CABIN1, SMCR8, A1BG, SUMO2, GDF15, GHR, GJB1, GCLM, GLUL, CXCR3, GPX7, GRIA3, GRIA4, GRIK1, GRIN2A, GRM3, CXCL1, GSK3B, HADHA, HDAC2, HEXA, HK1, HLA-B, MNX1, HLA-DRB1, HLA-DRB5, HLA-F, GJA1, GFRA1, ADAMTS3, GEM, ESR1, ESR2, ETS2, EZH2, F9, PTK2B, FGF1, FGF13, FKBP4, FKBP5, FMO3, AFF2, FPR2, FRAXE, FTH1, FTL, FZD2, GBA, GBAP1, GC, GCG, HMOX2, HNMT, HNRNPK, HP, ITGB2, ITPR1, ITPR2, ITPR3, JAG2, JAK3, KCNJ8, KCNJ11, KCNK2, KIF5B, KIR3DL1, LAMC1, LGALS2, LGALS4, LIF, FADS3, LTBR, LUM, SH2D1A, MARCKS, MAP1B, ISG20, IRF3, IRF1, IFRD1, HPGD, AGFG1, HES1, HSPA8, HSPB2, DNAJB1, HTC2, ID2, IFNGR1, IGFBP5, INPP5B, IGFBP7, IL1A, IL2, IL2RA, IL13, IL15, IL17A, IL18, CXCL10, EREG, EPHB1, ENG, CD36, BAG1, BAX, BBS2, CCND1, BMP4, BNIP1, BNIP3L, BRCA1, CACNA1A, CACNA1S, CALB1, CALB2, CALR, CAMK4, CAPG, CAPN1, CAPN2, CASR, CBR1, CBS, CD14, ATP7A, ATP5F1A, ARG1, ADH5, AOC1, ACAT2, ACHE, ACP3, ACTA1, ACTN3, ACY1, ADARB2, ADCYAP1R1, JAG1, FAS, AHR, AK4, ALOX5, ALOX15, AMPH, ANGPT1, APCS, APOA1, APOB, CD34, CD40, ELAVL4, CD59, CTSL, CYP1A1, CYP1A2, CYP2D6, CYP19A1, ACE, DCX, DDIT3, DDX3X, DHFR, DLD, DMD, DYNC1H1, DNMT3A, DPYD, DPYSL2, EFNA5, EFNB1, CELSR3, EGR1, ELAVL1, CTSD, CSNK1E, CSNK1D, TBCB, CD68, CDK2, CDK9, CDKN2A, CDKN2D, CEBPD, CTSC, CEACAM4, CHRNG, ABCC2, CRYM, CNR1, CNTFR, COL4A2, COL11A2, COL19A1, CORD1, MAP3K8, COX8A, CREB1, MB, MBP, MC4R, RNF112, TAT, TGFB2, TIMP1, TIMP2, TIMP3, CLDN5, TP73, TPO, NR2C2, TRN-GTT2-1, DNAJC7, UBC, UBE2H, UCP1, UCP3, SCGB1A1, UGCG, XDH, XPO1, XRCC1, XRCC5, MAP3K7, TACR1, TAC1, SOAT1, SHBG, SHH, SI, SLC1A3, SLC8A3, SLC12A2, SLC12A4, SUMO3, SERPINA3, SOD3, SYP, SOX5, SOX10, SPP1, SREBF1, SST, SULT1E1, STXBP1, SUPT4H1, ABCC8, YWHAZ, TUBA1A, SEL1L, CXCR4, MGAM, HSPB3, SELENBP1, UNC119, INA, P2RX6, SLC33A1, XPR1, KLF4, ZNHIT3, CD163, LONP1, KL, CHST2, GSTO1, MAP4K4, EIF2AK3, HOMER1, PICK1, ROCK2, ADAMTS4, RAB29, BCL10, CACNA1H, DYNLL1, SCG2, PABPN1, CDC7, GEMIN2, MAP4K3, PPM1D, FCN3, BLZF1, LGR5, TNKS, SYNJ2, DGAT1, TNFSF14, TNFRSF10B, IL18R1, PROM1, ASAP2, ALDH1A2, NR1I2, SYNJ1, SGK1, CX3CL1, DNAJB9, P2RY2, MYOD1, NAP1L1, CEACAM6, NCAM1, NEDD8, NEUROG1, NFIL3, NGFR, NONO, SLC11A2, NRF1, NRGN, NTF4, NTRK1, NTRK2, NTRK3, OPA1, OSBP, P2RX1, P2RX3, P2RX5, MYO6, MYH9, MYH6, MMP14, MDH1, MECP2, MEF2A, MEF2C, MAP3K5, MICE, MIF, MIP, MMP7, MPZ, MYC, MRC1, MS, MT1A, MT1B, ATP6, NUDT1, ND5, MUSK, MYBPH, P2RY1, PAH, CCL18, REG3A, PTPRN, PURA, RAB1A, RANGAP1, RBP4, REG1A, UPF1, REST, RET, TRIM27, ROS1, RPS17, RPS25, RPS27A, SORT1, S100A4, S100A8, S100A9, SCD, SCNN1A, CCL4, PTGER3, PTEN, PTAFR, PLEC, PAWR, PCBP1, PCSK2, SERPINF1, PFN2, PGK1, PHB, SERPINA1, PLCD1, PLP1, PSMA7, PLXNA2, POMC, POU5F1, PPID, PKN1, MAPK3, MAPK9, EIF2AK2, PSAP, H3P40

Drugs

(R)-troloxamide quinone, None, Allogeneic motor neuron progenitor cells derived from human embryonic stem cells ( MOTORGRAFT )

(R)-troloxamide quinone, None, Allogeneic motor neuron progenitor cells derived from human embryonic stem cells ( MOTORGRAFT ), Ambroxol hydrochloride, Arimoclomol, Autologous adipose derived mesenchymal stromal cells, Autologous bone marrow-derived mesenchymal stromal cells secreting neurotrophic factors, Autologous olfactory neural progenitors, Caprine hyperimmune serum against HIV lysate, DNA plasmid vector (pCK-HGFX7) expressing human hepatocyte growth factor, Dexpramipexole, Edaravone ( RADICAVA ), Enoxacin, Filgrastim ( GRASTOFIL, BIOGRASTIM, FILGRASTIM HEXAL, ACCOFIL, NEUPOGEN, NIVESTIM, TEVAGRASTIM, RATIOGRASTIM, ZARZIO ), H-Leu-Pro-Pro-Leu-Pro-Tyr-Pro-OH, Human culture expanded autologous mesenchymal stromal cells, Hydrocinnamate-[Orn-Pro-dCha-Trp-Arg]acetate, Ibudilast, Levosimendan, Masitinib mesilate, Olesoxime, Oligopeptide containing 6 amino acids (H-Phe-Ser-Arg-Tyr-Ala-Arg-OH), Recombinant human antibody directed against misfolded human superoxide dismutase 1, Recombinant human cerebral dopamine neurotrophic factor (CDNF), Recombinant human vascular endothelial growth factor, Recombinant humanised monoclonal antibody to human Nogo-A protein of the IgG1/kappa class, Reldesemtiv, Riluzole ( RILUTEK ), S[+] apomorphine, Sarsasapogenin, Smilagenin, Sodium chlorite, Sodium phenylbutyrate, tauroursodeoxycholic acid, Synthetic ribonucleic acid oligonucleotide directed against superoxide dismutase 1 (SOD-1) messenger ribonucleic acid, Talampanel, Tauroursodeoxycholic acid (TUDCA), Tirasemtiv, Xaliproden hydrochloride, adeno-associated viral vector serotype 9 encoding miRNA against human superoxide dismutase 1

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A number sign (#) is used with this entry because this form of autosomal dominant ALS is caused by mutation in the FIG4 gene (609390).

Autosomal recessive Charcot-Marie Tooth disease type 4J (CMT4J; 611228) is an allelic disorder with a much more severe phenotype.

For a general phenotypic description and a discussion of genetic heterogeneity of amyotrophic lateral sclerosis (ALS), see ALS1 (105400).

Clinical Features

Chow et al. (2009) reported 5 unrelated patients diagnosed with probable or definite ALS. Two had a family history of the disorder. All had adult onset and showed prominent corticospinal tract findings. Nerve conduction velocity studies were normal, but EMG studies showed some denervation.

Molecular Genetics

In 5 unrelated patients with amyotrophic lateral sclerosis, Chow et al. (2009) identified heterozygosity for a missense, 2 splice site, and 2 truncating mutations in the FIG4 gene (see, e.g., 609390.0006-609390.0008). The mutations were shown to result in complete or highly significant loss of protein function. Five different missense FIG4 mutations were identified in 5 patients with a diagnosis of ALS or adult-onset primary lateral sclerosis (PLSA1; 611637), but these mutations were not clearly shown to be pathogenic.