Gendia | Next Generation Sequencing Platforms

Next Generation Sequencing Platforms

Heterogeneous diseases like Noonan syndrome, hypertrophic cardiomyopathy, dilated cardiomyopathy, deafness, Usher syndrome, retinitis pigmentosa, Brugada syndrome, Long QT syndrome, Arrhythmogenic Right Ventricular Cardiomyopathy, Polymorphic Ventricular Tachycardia, spastic paraplegia, Parkinson syndrome, Charcot-Marie-Tooth disease, mental retardation, etc can be caused by a multitude of genes.
Diagnostic molecular testing for these heterogeneous diseases is complicated and expensive if it follows a gene-after-gene classical approach.
Next generation sequencing platforms however allow the parallel sequencing of billions of nucleotides, so that large panels of genes can be sequenced in the same sequencing run. This new technology makes molecular testing for heterogeneous diseases cheap and fast.

Disease	Genes	Comment
AORTIC ANEURYSM	ACTA2 CBS FBN1 FBN2 MYH11 COL3A1 SLC2A10 SMAD3 TGFBR1 TGFBR2	10 genes
ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY (ARVC)	Ryanodine receptor 2 (RYR2) for ARVC2 Transmembrane protein 43 (TMEM43) for ARVC5 Desmoplakin (DSP) for ARVC8 Plakophilin-2 (PKP2) for ARVC9 Desmoglein-2 (DSG2) for ARVC10 Desmocollin-2 (DSC2) for ARVC11 Junction plakoglobin (JUP) for ARVC12	7 genes
ATRIAL FIBRILLATION	GJAS KCNA5 KCNE2 KCNQ1 NPPA	5 genes
AUTOSOMAL RECESSIVE AND SPORADIC RETINITIS PIGMENTOSA	USH2A (Usherin) EYS (Eyes Shut Homolog) ABCA4 (ATP-binding cassette, subfamily A, member 4) CRB1 (Crumbs homologue 1) PDE6A (Phosphodiesterase 6A, cGMP-specific, rod alpha subunit) PDE6B (Phosphodiesterase 6B, cGMP-specific, rod beta subunit) RPE65 (Retinal pigment epithelium-specific protein, 65-kd)	7 genes
BRUGADA SYNDROME	SCN5A (Brugada Syndrome, Type 1) GPD1L (Brugada syndrome, Type 2) CACNA1C (Brugada syndrome, Type 3) CACNB2 (Brugada syndrome, Type 4) SCN1B (Brugada syndrome, Type 5)	5 genes
CANCER	BRCA1 BRCA2 CHEK2 PALB2 BRIP1 BARD1 CDH1 ATM TP53 PTEN STK11 RAD50 RAD51C MRE11A NBN	15 cancer genes
CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA (CPVT)	Cardiac ryanodine receptor channel (RYR2 gene with 105 exons) for CPVT1 Calsequestrin (CASQ2 gene with 11 exons) for CPVT2	2 genes
COMPLEX IV GENE PANEL	COX6B1 COX10 COX15 SCO1 SCO2 SURF1 TACO1	7 genes
CONGENITAL DISORDER OF GLYCOSYLATION (CDG)	ALG2 ALG3 ALG6 ALG8 ALG9 ALG12 ATP6V0A2 B4GALT1 COG1 COG7 COG8 DK1(DOLK) DPAGT1 DPM1 GNE LEC2(SLC35A1) MGAT2 MOGS(GCS1) MPDU1 MPI PMM2 RFT1 SLC35C1 TUSC3	24 genes
CONGENITAL MUSCULAR DYSTROPHIES	COL6A1 COL6A2 COL6A3 FKRP FKTN ITGA7 LAMA2 LARGE POMGNT1 POMT1 POMT2 SEPN1	12 genes
DEMENTIA AND AMYOTROPHIC LATERAL SCLEROSIS	ALS2 ANG APOE APP CHMP2B DCTN1 FIG4 FUS MAPT OPTN PRGN PSEN1 PSEN2 SETX SOD SORL1 TARDBP VABP VCP	19 genes
DILATED CARDIOMIOPATHY (DCM)	Myosin heavy chain (MYH7) Troponin T (TNNT2) Myosin-binding protein C (MYBPC3) Troponin I (TNNI3) Tropomyosin 1 (TPM1) Actin (ACTC) Lamin A/C (LMNA) Z-band alternatively spliced PDZ motif-containing protein (ZASP) Tafazzin (TAZ) Phospholamban (PLN) Lysosome-associated membrane protein 2 (LAMP2) Transthyretin (TTR) Delta-sarcoglycan (SGCD) Desmin (DES) 10 Mitochondrial transfer RNA’s for leucine1/ leucine2 / glutamine /histidine / aspartic acid / isoleucine/ methionine/ lysine / serine1 / serine2 (MTTL1, MTTL2, MTTQ, MTTH, MTTD, MTTI, MTTM MTTK, MTTS1, MTTS2) 3 Mitochondrial complex 1 subunits ND1, ND5 and ND6 (MTND1, MTND5, and MTND6)	27 DCM genes
FAMILIAL AORTOPATHIES	FBN1 gene encoding fibrillin 1 for Marfan syndrome, MASS (mitral valve, aorta, skeleton, and skin) syndrome, isolated ectopia lentis, Weill-Marchesani syndrome, and Shprintzen-Goldberg syndrome TGFBR2 gene encoding transforming growth factor-beta receptor, type 2 for Loeys-Dietz Syndrome, Marfan-like syndrome (Marfan syndrome type 2), Ehlers-Danlos syndrome type 4, and Thoracic Aortic Aneurysms FBN2 gene encoding fibrillin 2 for Beals syndrome (congenital contractural arachnodactyly)	3 genes
FAMILIAL ARRYTHMIA	AKAP9 ANK2 CACNA1C CACNB2 CASQ2 CAV3 DSC2 DSG2 DSP GPD1L JUP KCNA5 KCNE1 KCNE2 KCNE3 KCNH2 KCNJ2 KCNQ1 NPPA PKP2 PLN RYR2 SCN1B SCN3B SCN4B SCN5A SNTA1 TGFB3 TMEM43	29 genes
FAMILIAL CARDIOMYOPATHY	ABCC9 ACTC1 ACTN2 CALR3 CAV3 CSRP3 DES DSG2 DTNA EYA4 FKTN JPH2 LAMP2 LDB3 LMNA MIOZ2 MYBPC3 MYH6 MYH7 MYL2 MYL3 MYLK2 NEXN PLN PRKAG2 PSEN1 PSEN2 RBM20 SCN5A SGCD SLC25A4 TAZ TCAP TMPO TNNC1 TNNT2 TPM1 TNNI3 TTN VCL	40 genes
HYPERTROPHIC CARDIOMIOPATHY (HCM)	Myosin-binding protein C (MYBPC3) Regulatory and Essential light chains (MYL2, MYL3) Myosin heavy chain (MYH7) Actin (ACTC) Tropomyosin 1 (TPM1) Troponin I (TNNI3) Troponin C (TNNC1) Troponin T (TNNT2) Caveolin 3 (CAV3) Noncatalytic AMP-activated protein kinase gamma 2 (PRKAG2) Lysosome-associated membrane protein 2 (LAMP2) Alpha galactosidase (GLA) Transthyretin (TTR)	17 HCM genes with a detection rate of at least 60% in HCM
LEIGH SYNDROME PANEL	BCS1L COQ2 COX10 COX15 DLD PDHA1 SCO2 SURF1 TACO1	9 genes
LONG QT SYNDROME (LQT1-12)	KCNQ1 encoding KQT-like voltage-gated potassium channel 1 for LQT1 KCNH2 encoding Potassium channel, voltage-gated, H2 for LQT SCN5A encoding Alpha polypeptide of voltage-gated sodium channel type V for LQT3 ANK2 encoding Ankyrin-B for LQT4 KCNE1 encoding Voltage-gated potassium channel, Isk related subfamily, member 1 for LQT5 KCNE2 encoding Voltage-gated potassium channel, Isk related subfamily, member 2 for LQT6 KCNJ2 encoding Inwardly rectifying potassium channel for LQT7 CACNA1C encoding Calcium channel, L type, alpha 1 polypeptide isoform for LQT8 CAV3 encoding Caveolin 3 for LQT9 SCN4B encoding Sodium channel, voltage-gated, type IV beta subunit for LQT10 AKAP9 encoding A-kinase anchor protein-9 for LQT11 SNTA1 encoding alpha-1 syntrophin gene for LQT12	12 genes (LQT1-LQT12)
MITOCHONDRIAL DISEASE	MTRNR1 MTRNR2 MTND1 MTND2 MTND3 MTND4L MTND4 MTND5 MTND6 MTCO1 MTCO2 MTCO3 MTATP8 MTATP6 MTCYB MTTF MTTV MTTL1 MTTI MTTQ MTTM MTTW MTTA MTTN MTTC MTTY MTTS1 MTTD MTTK MTTG MTTR MTTH MTTS2 MTTL2 MTTE MTTT MTTP	Entire mitochondrial genome (16569 bp) including all the 37 genes (2 rRNA genes, 22 tRNA genes, and 13 protein-coding genes) and non-coding regions
MITOCHONDRIAL DISEASES DUE TO MUTATIONS IN NUCLEAR GENES	BCS1L COQ2 COX6B1 COX10 COX15 DGUOK DLD MPV17 OPA1 PDHA1 PEO1 (C10ORF2, Twinkle) POLG (POLG1) POLG2 RRM2B SCO1 SCO2 SLC25A4 (ANT1) SUCLA2 SUCLG1 SURF1 TACO1 TK2 TIMM8A (DDP1) TYMP (ECGF1, TP)	24 genes
mtDNA DEPLETION SYNDROME	DGUOK MPV17 OPA1 PEO1 (C10ORF2, Twinkle) POLG (POLG1) POLG2 RRM2B SLC25A4 (ANT1) SUCLA2 SUCLG1 TK2 TYMP (ECGF1, TP)	12 genes
NOONAN, LEOPARD, COSTELLO and CARDIOFACIOCUTANEOUS SYNDROME	PTPN11 SOS1 RAF1 BRAF MAP2K1 MAP2K2 HRAS KRAS SHOC2	9 genes
PARKINSON DISEASE	DJ1 LRRK2 PARK2 PINK1 SNCA	5 genes
PEO PANEL	OPA1 PEO1 (C10ORF2, Twinkle) POLG (POLG1) POLG2 RRM2B SLC25A4 (ANT1)	6 genes
PERIODIC FEVER SYNDROMES	ELANE (ELA2) LPIN2 MEFV MVK NLRP3 (CIAS1) PSTPIP1 TNFRSF1A	7 genes
PRIMARY CILIARY DYSKINESIA	DNAAF1/LRRC50 DNAAF2/c14orf104 DNAH5 DNAH11 DNAI1 DNAI2 RSPH4A RSPH9 TXNDC3 OFD1 RPGR CFTR	12 genes
SHORT QT SYNDROME	CACNA1B CACNA1C KCNH2 KCNJ2 KCNQ1	5 genes
STARGARDT DISEASE 1, CONE-ROD DYSTROPHY, RETINITIS PIGMENTOSA, FUNDUS FLAVIMACULATUS, AGE-RELATED MACULAR DYSTROPHY	ABCA4 (ABCR)	1 gene
SUDDEN DEATH	ABCC9 ACTC1 ACTN2 AKAP9 ANK2 CACNA1B CACNA1C CACNB2 CALR3 CASQ2 CAV3 CSRP3 DES DSC2 DSG2 DSP DTNA EYA4 FBN1 FBN2 FKTN GJA5 GPD1L JPH2 JUP KCNA5 KCNE1 KCNE2 KCNE3 KCNH2 KCNJ2 KCNQ1 LAMP2 LDB3 LMNA LRP6 MEFA2 MYBPC3 MYH6 MYH7 MYL2 MYL3 MYLK2 MYOZ2 NEXN NPPA PKP2 PLN PRKAG2 PSEN1 PSEN2 RBM20 RYR2 SCN1B SCN3B SCN4B SCN5A SGCD SLC25A4 SNTA1 TAZ TCAP TGFB3 TGFBR2 TMEM43 TMPO TNNC1 TNNI3 TNNT2 TPM1 TTN VCL	72 genes
USHER SYNDROME and NON-SYNDROMIC DEAFNESS	USHER TYPE 1 MYO7A encoding Myosin 7A for Usher syndrome type 1A/B (USH1A/B) USH1C encoding Harmonin for Usher syndrome type 1C (USH1C) CDH23 encoding Cadherin23 for Usher syndrome type 1D (USH1D) PCDH15 encoding Protocadherin15 for Usher syndrome type 1F (USH1F) USH1G encoding Usher syndrome type-1G protein for Usher syndrome type 1G (USH1G) USHER TYPE 2 USH2A encoding Usherin for Usher syndrome type 2A (USH2A) GPR98 (exons 8, 20, 31-41 & 89) encoding the G-protein-coupled 7-transmem-brane receptor for for Usher syndrome type 2C (USH2C) WHRN encoding Whirlin for Usher syndrome type 2D (USH2D) USHER TYPE 3 CLRN1 encoding Clarin 1 for Usher syndrome type 3A (USH3A) NON-SYNDROMIC DEAFNESS GJB6 MYO6 OTOF SLC26A4 (PDS) TMC1 TMIE TMPRSS3 TMC1 MTTS (tRNAser(UCN)) MTRNR1 (6 mutations in 12S rRNA)	19 genes
USHER SYNDROME AND RETINITIS PIGMENTOSA	USH2A encoding Usherin	USH2A next generation sequencing with del/dup testing (Targeted aCGH)
X-LINKED MENTAL RETARDATION	ABCD1 ACSL4 AFF2 AGTR2 AP1S2 ARHGEF6 ARHGEF9 ARX ATP6AP2 ATP7A ATRX BCOR BRWD3 CASK CDKL5 CUL4B DCX DKC1 DLG3 DMD FANCB FGD1 FLNA FMR1 FTSJ1 GDI1 GK GPC3 GRIA3 HCCS HPRT HSD17B10 HUWE1 IDS IGBP1 IL1RAPL1 JARID1C KIAA2022 KLF8 L1CAM LAMP2 MAGT1 MAOA MBTPS2 MECP2 MED12 MID1 MTM1 NDP NDUFA1 NHS NLGN3 NLGN4 NSDHL NXF5 OCRL OFD1 OPHN1 OTC PAK3 PCDH19 PDHA1 PGK1 PHF6 PHF8 PLP1 PORCN PQBP1 PRPS1 RAB39B RPL10 RPS6KA3 SHROOM4 SLC16A2 SLC9A6 SMC1A SMS SOX3 SRPX2 SYN1 SYP TIMM8A TM4SF2 TSPAN7 UBE2A UPF3B ZCCHC12/SIZN2 ZDHHC15 ZDHHC9 ZNF41 ZNF674 ZNF711 ZNF81	93 genes