Primary Outcomes

Description: Next-Generation Sequencing (NGS) of the GBA gene will be performed. The mutation will be confirmed by Sanger sequencing.

Measure: Sequencing of the Gaucher disease related gene

Time: 4 weeks

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Secondary Outcomes

Description: The quantitative determination of small molecules (molecular weight 150-700 kD, given as ng/μl) within a dried blood spot sample will be validated via liquid chromatography multiple reaction-monitoring mass spectrometry (LC/MRM-MS) and compared with a merged control cohort. The statistically best validated molecule will be considered as a disease specific biomarker.

Measure: The Gaucher disease specific biomarker candidates finding

Time: 24 months

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HP:0002240: Hepatomegaly

Genes 682

CCDC47 TCIRG1 LBR RAG1 INSR CPT2 CDIN1 CPOX PHKA2 SGSH EPB42 SLC22A5 TSFM LYZ ND2 KCNN4 COG7 GPC3 LIG4 RRAS2 OSTM1 APOA1 CTSK CASP10 CC2D2A PDGFRA DPM2 ERBB3 PCCB MOGS ASAH1 NDUFAF1 BOLA3 GPR35 ATP6V1B2 ZAP70 RAG2 WRAP53 ADA2 TTC37 KCNH1 KLF1 LTBP3 PHKB CLCA4 SAA1 RNASEH2A PEX1 ALG2 PIEZO1 FAH NDUFS3 AUH IL6 NDUFV2 TNNT2 PRKCSH HBG2 ERCC8 ALDH7A1 PHKG2 PEX6 ATP8B1 LIPE TCF4 RUNX1 MPV17 CTLA4 NLRP3 SLC7A7 GBA NDUFB11 ICOS MYBPC3 SLC37A4 CYBC1 VPS33A DLD BSCL2 HSD3B7 MYD88 GBA KCNH1 TRNW PEX1 MRAS CIDEC PCCA PEX10 AGL DHFR GPC4 TIMMDC1 OCLN NDUFAF8 NDUFB10 CLDN1 GLB1 TMEM70 FASLG ASL ACADVL COX8A PLAGL1 STX11 AGA LMNA DAXX HGSNAT AP3D1 PEX1 AGGF1 LIPA RPGRIP1L LARS1 MARS1 RAG2 SLC25A20 PSMB8 CLCN7 MST1 PEX12 TRAPPC11 NCF4 NDUFS6 ARSB LYST FOXRED1 RAG1 INPPL1 TNFSF11 XIAP XPR1 HBG1 F5 ABHD5 ITCH NDUFAF4 FOS IL2RG HFE B2M CLCN7 PDGFRB HYMAI FAS GNPTAB TRAPPC11 GBA IGF2 PPARG DHDDS MET AGPAT2 GLRX5 TNNI3 TINF2 RHAG HSD17B4 DCLRE1C VPS45 ATP8B1 HSD3B7 APOE ANK1 PEX1 ACAT1 PMM2 ND5 PEX16 PPARG SOS2 HADHA NDUFS8 NAGS NDUFAF3 PEX11B TMEM126B NPC1 PEX6 PCCB GPIHBP1 PEX14 PEX5 CAV1 PRF1 LPIN2 GPC1 SNX10 ERCC6 IL2RG COX6B1 PCCA MMAA CPT1A PEX12 GPC4 KRT16 HNF1A HBB CLCN7 NCF2 XRCC4 SRP54 TET2 COX14 IDUA ATP7B SUMF1 DGUOK ALG13 ACOX1 EXTL3 NCF1 NLRP1 COG6 DCDC2 HLA-DRB1 CASR SLC25A15 RMRP FUCA1 SKIV2L GLB1 GLIS3 PEX26 COA3 G6PC DCDC2 PEX12 FERMT3 LBR RAB27A HBB NDUFS2 CALR NDUFV1 PEX5 TNFRSF13C NEU1 SCYL1 UCP2 STEAP3 PCK1 PEX19 DOLK MRPL3 MYPN IDS SBDS ACADM HBB SOS1 LCAT STX1A WDR35 CCDC115 DPM1 CYBB IDUA HMGCS2 TERT CR2 GAA CYTB FBP1 ALMS1 IL2RB ETFDH JAK2 BMP2 PEX2 SLC22A5 GNMT HJV HMGCL SMPD1 NDUFAF2 PLEKHM1 KCNQ1OT1 TRNL1 RNU4ATAC RMRP PRKCD SLC4A1 TALDO1 RAF1 DDRGK1 ND3 PIK3C2A CAV1 PEX13 CPT2 SF3B1 TRNW CPT1A NDUFB3 ND6 DCLRE1C PSMB4 CDKN1C JAK2 AGA TET2 PIGS COX20 FGA RIT1 PYGL NCF1 IL2RA TMEM67 SLC7A7 CAVIN1 GBA NGLY1 MFN2 BSCL2 KCNQ1 TRMU CLDN1 CTNS PEPD FAS SLC2A1 H19-ICR HAMP MMUT ALG8 CTC1 IFT122 PEX2 KRT6A XYLT1 FLNC TNFRSF1B GPC3 NDUFS7 ACADM RAG1 HBA2 TNFRSF1B GBA CYBA CBL SCO1 NDUFAF5 SPTB G6PC3 AMACR PSAP SC5D IFT172 SLC25A13 NOP10 MPI EIF2AK3 NGLY1 SEC63 PEX16 PIGM A2ML1 TACO1 TRNE CD19 CASR ALMS1 TREX1 ATRX CPT2 SLC39A4 ND3 SLCO2A1 HBB CPT2 APOE PET100 ABCA1 GCDH GNE RFT1 PEX26 SCARB2 HFE SEC63 HYOU1 GNS TNFRSF11A PEX5 SLC25A20 ATPAF2 TUFM BSCL2 PSAP DCTN4 COG4 ALDOB DDRGK1 CD40LG IFT140 ABCB11 ND1 PEX26 AKR1D1 NPHP3 COX10 C1QBP AKR1D1 CFTR CC2D2A SMPD1 RFT1 PEX3 PC NAGA MMUT BTNL2 TRIM37 SLC25A1 ACOX1 USP18 NRAS PEX19 FBN1 NDUFS1 PDGFB ALG9 MYORG RHBDF2 HBA1 TTC37 CD28 LIG4 MCM4 GALNS NPC2 GBA IL7R TMEM67 PTRH2 NAGLU COA8 LMNA MAN2B1 HMGCL KCNJ11 ALDOB SLC30A10 SP110 ATP6 GPD1 PEX12 SMPD1 ACADL SLC13A5 NHLRC2 TRMU HBG2 ABCC8 HADHA PEX13 HNF4A FAS TMEM165 PIGA PTPRC ABCC2 TCIRG1 NRAS PNPLA2 APOC2 ADA ABCB4 RTEL1 CYP7B1 ABCD3 EWSR1 ATP6AP1 UQCRB ND1 NDUFS4 SNX10 ABHD5 CBL CTLA4 ASXL1 ETFA LRP5 SLC29A3 DYNC2LI1 PEX2 EARS2 ASS1 TRNN FBP1 NEK8 GBA MPL ADAMTSL2 SLC25A13 MRPS7 CTNNB1 CYP7B1 TGFB1 COA8 EFL1 RMND1 SBDS CAVIN1 ADA MVK ICOS FAM111B PYGL LBR GALT NOTCH2 MMUT PEX3 PKHD1 GNE PEX11B BSCL2 ETFB FAH PSMB9 SLC17A5 INPP5E IDUA YARS2 TRNS1 RBCK1 GBA MVK TET2 RAG2 HLA-DRB1 CASP10 MMAB KCNN3 RASA2 CA2 ATP7B XIAP DNASE1L3 POLG RASGRP1 PEX6 SLC30A10 ANTXR1 NAGA COG5 NPM1 SLC37A4 NDUFA6 MIF SLC25A19 POLG2 MEFV CBS DNAJC21 COX4I2 SKIV2L SOX10 AKT2 VPS13A MPL HMOX1 WT1 HNF4A GBA TKFC DIS3L2 KRAS NDUFS4 BTNL2 LMNA LMNA SH2D1A KLF1 HBA2 CYBA SRP54 ABCB11 ALG1 NDUFA1 CHD7 SLC25A15 GATA2 NDUFA11 CD96 TERC TNFRSF13B CD28 MPC1 RPGRIP1L SERPINA1 JAM3 LZTR1 KRT17 SRSF2 PTPN11 IL2RG CIDEC PHKG2 NCF2 NDUFAF1 ND4 GFM1 PARN NLRP3 TRIM37 GUCY2D PEX10 POLD1 PEX14 PEPD SPTA1 DLD HBA1 ACADVL TRNK CD70 FASLG DGUOK SLC20A2 ND2 AGPAT2 PEX10 CYBB PEX6 IL1RN CTLA4 DNAJC21 NDUFB9 LIPA PHKA2 ITK KIF20A LYST SUMF1 NHP2 HLA-DRB1 TRNV CD27 PEX16 PEX3 SLC25A19 IL7R RRAS HPGD EIF2AK3 PLPBP CD55 IDUA TKT USB1 LACC1 KRT6B PTEN BTD IFIH1 GALE NDUFS7 PRKCD PNPLA2 AMACR PEX14 TGFB1 DKC1 IDUA JAM2 GUSB EFL1 AP3B1 LIPA TET2 JAK2 FUCA1 NUBPL FDX2 KRAS

Protein Mutations 4

L444P N370S R463C R496H

HP:0001744: Splenomegaly

Genes 484

CCDC47 ATRX TCIRG1 RAG1 CDIN1 CPOX JAK2 BACH2 SGSH EPB42 MVK PTEN SH2B3 LYZ KCNN4 COG7 GPC3 PEX7 MEFV OSTM1 APOA1 IL12A-AS1 CTSK CASP10 SPTB CC2D2A PDGFRA ERBB3 RUNX1 ASAH1 GPR35 CD81 THPO ATP6V1B2 ZAP70 RAG2 WRAP53 ADA2 TTC37 EPB41 KCNH1 KLF1 IGH RNASEH2A LAT CCR1 PIEZO1 FAH IL6 CCND1 KLRC4 ERCC8 GATA1 PHKG2 TNFRSF13B TCF4 RUNX1 TP53 MPIG6B CTLA4 NLRP3 SLC7A7 CALR GBA ICOS SH2B3 ALAS2 CYBC1 VPS33A BSCL2 HSD3B7 MYD88 PKLR GBA BCL2 KCNH1 PHYH GP1BA GPC4 OCLN CASK CLDN1 FASLG HAVCR2 THPO GATA1 STX11 NBEAL2 LMNA HGSNAT C4A AP3D1 ATM LIPA RPGRIP1L NOD2 ARVCF BPGM PSMB8 CLCN7 JAK2 MST1 NCF4 ARSB LYST TPP2 INPPL1 TNFSF11 XIAP HBG1 F5 ITCH FOS MPL HFE B2M CLCN7 FAS GNPTAB GBA JAK2 PPARG AGPAT2 GLRX5 TINF2 RHAG DCLRE1C VPS45 ATP8B1 HSD3B7 APOE ANK1 ABCA1 USB1 UFD1 PPARG FAS NPC1 GPIHBP1 CAV1 IL12A ICOS PRF1 LPIN2 NLRC4 GPC1 SNX10 PIK3R1 ERCC6 GPC4 HBB IRF8 CLCN7 NCF2 TET2 IDUA DHCR24 SUMF1 DGUOK NCF1 NLRP1 COG6 COMT DCDC2 HLA-DRB1 CASR RMRP FUCA1 SKIV2L GLB1 JMJD1C GLIS3 KCNN4 IL23R DCDC2 FERMT3 LBR RAB27A ERAP1 HBB PKLR CALR TNFRSF13C NEU1 SCYL1 SPTB HIRA STEAP3 TNFRSF4 AKT1 DOLK CCND1 CARD11 OTC IDS SH2B3 BCR LCAT WDR35 CCDC115 DPM1 CYBB IDUA TERT CR2 G6PD GAA HLA-B MKS1 ALMS1 IL2RB JAK2 BMP2 PEX2 HJV MEFV SMPD1 MVK FOXP3 PLEKHM1 RNU4ATAC PRKCD SLC4A1 CFAP410 TALDO1 DDRGK1 PIK3C2A CAV1 SF3B1 PIEZO1 HK1 TBX1 CCBE1 HBB DCLRE1C PSMB4 JAK2 AGA GBA TET2 FGA NCF1 CR2 SLC4A1 IL2RA TMEM67 UMPS CAVIN1 GBA SEC24C BSCL2 NFKB2 CTNS HLA-DRB1 PEPD FAS SLC2A1 HAMP ABL1 PRKCD CTC1 TNFRSF1B EPB42 GPC3 RAG1 HBA2 TNFRSF1B NLRP12 GBA CYBA JAK2 CBL SPTB G6PC3 PSAP IFT172 NOP10 NGLY1 PIGM CD19 CASR TREX1 GUSB SLC39A4 SLCO2A1 EPB41 HBB ABCA1 GNE GFI1B SCARB2 HFE GNS CALR TNFRSF11A UROS CD19 PSAP COG4 RREB1 DDRGK1 CD40LG ABCB11 AKT1 AKR1D1 AKR1D1 CC2D2A SMPD1 BTNL2 ABCG8 NRAS TNFRSF13C BCL6 HBA1 CD28 LIG4 MCM4 NPC2 GBA IL7R TMEM67 NAGLU MAN2B1 ANK1 RASGRP1 ANK1 GPD1 SMPD1 TNFRSF1A HBG2 UBAC2 FAS TPI1 APOE NEU1 PTPRC TCIRG1 APOC2 SPTA1 ADA ABCB4 RTEL1 CYP7B1 ABCD3 PTEN ATP6AP1 SNX10 CTLA4 ASXL1 SAMD9L PNP SLC29A3 DYNC2LI1 NOTCH1 GYPC GBA MPL GP1BB TLR4 CYP7B1 CAVIN1 ADA MVK ICOS FMO3 SLC4A1 NOTCH2 IGH MMUT PKHD1 RHAG FAH PSMB9 SLC17A5 INPP5E IDUA NFKB1 GBA TET2 RAG2 HLA-DRB1 CASP10 KCNN3 CA2 ATP7B XIAP DNASE1L3 GNPTAB MS4A1 IL10 BRAF IFNGR1 RASGRP1 SLC30A10 RAG1 NPM1 MIF STAT4 SH2B3 SEC23B MEFV NBEAL2 UROS COX4I2 MPL SOX10 VPS13A MPL PIK3CA ADAMTS3 GBA LMNA SH2D1A KLF1 HBA2 CYBA ALG1 TBX1 CHD7 MPL GATA2 TERC CALR TNFRSF13B CD28 HBB RPGRIP1L LPL SRSF2 IL2RG PHKG2 JAK2 NCF2 PARN NLRP3 PIK3CD PEPD SPTA1 GPI HBA1 FASLG DGUOK PIEZO1 AGPAT2 CYBB IL1RN CTLA4 LIPA TNFSF12 PHKA2 ITK CDAN1 LYST SUMF1 APOA1 NHP2 CD27 CASP8 IL7R TNFSF12 HPGD IDUA SLC4A1 USB1 LACC1 PTEN TET2 TBXAS1 BTD IFIH1 GALE PRKCD TGFB1 FAT4 DKC1 IDUA ALDOA GATA1 GUSB AP3B1 LIPA TET2 JAK2 KRAS

Protein Mutations 5

L444P N370S R463C R496H V617F