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
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
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
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
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 TGFBR1 gene encoding transforming growth factor-beta receptor, type 1 for Loeys-Dietz Syndrome, Marfan-like syndrome (Marfan syndrome type 2), and Ehlers-Danlos syndrome type 4 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 COL3A1 gene encoding Collagen 3 for Ehlers-Danlos syndrome type 4 ACTA2 gene encoding aortic smooth muscle actin for Thoracic Aortic Aneurysms MYH11 gene encoding Myosin 11 for Thoracic Aortic Aneurysms	6 genes
FAMILIAL ARRYTHMIA	ANK2 encoding Ankyrin-B CACNA1C encoding Calcium channel, L type, alpha 1 CACNB2 encoding Calcium channel, voltage-dependent, beta 2 CASQ2 encoding Calsequestrin CAV3 encoding Caveolin 3 DSC2 encoding Desmocollin-2 DSG2 encoding Desmoglein-2 DSP encoding Desmoplain GPD1L encoding Glycerol-3-phosphate dehydrogenase 1-like JUP encoding Junction plakoglobin KCNE1 encoding Voltage-gated potassium channel, Isk related, member 1 KCNE2 encoding Voltage-gated potassium channel, Isk related, member 2 KCNH2 encoding Potassium channel, voltage-gated, H2 KCNJ2 encoding Inwardly rectifying potassium channel KCNQ1 encoding KQT-like voltage-gated potassium channel 1 NPPA encoding Natriuretic peptide precursor a PKP2 encoding Plakophilin-2 PLN encoding Phospholamban RYR2 encoding Ryanodine receptor 2 SCN1B encoding Sodium channel, voltage-gated, type 1B SCN4B encoding Sodium channel, voltage-gated, type 4B SCN5A encoding Sodium channel, voltage-gated, type 5A TGFB3 encoding Transforming growth factor, beta 3 TMEM43 encoding Transmembrane protein 43	24 genes
FAMILIAL CARDIOMYOPATHY	ABCC9 gene encoding ATP-binding cassette, subfamily c, member 9 ACTC1 gene encoding cardiac actin ACTN2 gene encoding actinin, alpha-2, ALMS1 gene encoding Alstrom syndrome protein APOA1 gene encoding apolipoprotein A1 CAV3 gene encoding caveolin 3 CSRP3 gene encoding cysteine- and glycine-rich protein 3 CTF1 gene encoding cardiotrophin DES gene encoding desmin DNAJC19 gene encoding DNAJ/HSP40 homolog, subfamily c, member 19 DSC2 gene encoding desmocollin-2 DSG2 gene encoding desmoglein-2 DSP gene encoding desmoplakin DTNA gene encoding dystrobrevin, alpha EMD gene encoding emerin FKTN gene encoding fukutin GLA gene encoding alpha galactosidase HOPX gene encoding hop homeobox JUP gene encoding junction plakoglobin LAMP2 gene encoding lysosome-associated membrane protein 2 LDB3 gene encoding lim domain-binding 3 LMNA gene encoding lamin A/C MTND1, MTND5, and MTND6 gene encoding 3 Mitochondrial complex 1 subunits ND1, ND5 and ND6 MTTG, MTTI, MTTL1, MTTQ, MTTH, MTTK, MTTS1 and MTTS2 gene encoding 8 Mitochondrial transfer RNAs MYBPC3 gene encoding myosin-binding protein C MYH6 gene encoding myosin heavy chain 6 MYH7 gene encoding myosin heavy chain 7 MYL2 gene encoding myosin, light chain 2 MYL3 gene encoding myosin, light chain 3 MYLK2 gene encoding myosin light chain kinase 2 PKP2 gene encoding plakophilin-2 PLN gene encoding phospholamban PRKAG2 gene encoding noncatalytic AMP-activated protein kinase gamma 2 RYR2 gene encoding ryanodine receptor 2 SCN5A gene encoding sodium channel, voltage-gated, type v, alpha subunit SGCD gene encoding delta-sarcoglycan TAZ gene encoding tafazzin TCAP gene encoding titin-cap TGFB3 gene encoding transforming growth factor, beta-3 TMEM43 gene encoding transmembrane protein 43 TMPO gene encoding thymopoietin TNNC1 gene encoding troponin C TNNI3 gene encoding troponin I TNNT2 gene encoding troponin T TPM1 gene encoding tropomyosin 1 TTN gene encoding titin TTR gene encoding transthyretin VCL gene encoding vinculin	57 genes
FAMILIAL HYPERCHOLESTEROLEMIA	LDLR gene encoding low density lipoprotein receptor for Familial hypercholesterolemia type 2A APOB gene encoding apolipoprotein B for ligand-defective apolipoprotein B-100 hypercholesterolemia and familial hypobetalipoproteinemia ABCA1 gene encoding ATP-binding cassette transporter 1 for Tangier disease and familial high density lipoprotein deficiency APOA2 gene encoding apolipoprotein A2 for familial apolipoprotein A2 deficiency APOC3 gene encoding apolipoprotein C3 for familial apolipoprotein C3 deficiency PCSK9 gene encoding proprotein convertase subtilisin/kexin type 9 for autosomal dominant hypercholesterolemia type 3 PON2 gene encoding paraoxonase 2 for coronary heart disease	7 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
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) 6 Mitochondrial transfer RNAs for leucine/glutamine/histidine/lysine/ serine1/serine2 (MTTL1, MTTQ, MTTH, MTTK, MTTS1 and MTTS2) 3 Mitochondrial complex 1 subunits ND1, ND5 and ND6 (MTND1, MTND5, and MTND6)	23 DCM genes
LONG QT SYNDROME (LQT1-10)	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	10 genes (LQT1-LQT10)
NOONAN, LEOPARD, COSTELLO and CARDIOFACIOCUTANEOUS SYNDROME	PTPN11 SOS1 RAF1 BRAF MAP2K1 MAP2K2 HRAS KRAS	8 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