Validation of Ion TorrentTM Inherited Disease Panel with the PGMTM Sequencing Platform for Rapid and Comprehensive Mutation Detection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Samples
2.2. Library Building and Sequencing
2.3. Data Analysis
2.4. Tertiary Analysis and Variant Validation
3. Results
3.1. Sequencing Quality, Coverage and Overall Panel Performance
3.2. Variant Calling
3.3. Variant Detection Yield
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Clinical Diagnosis | Abbreviation | Category | Genes Included in the Panel | OMIM# |
---|---|---|---|---|
Agammaglobulinemia, X-linked, Type I | XLA | Immunodeficiency | BTK | 300755 |
Argininosuccinate Lyase Deficiency | ASA | Metabolic disorder | ASL | 207900 |
Arylsulfatase A Deficiency | AAD | Leukodystrophy | ARSA | 250100 |
Ataxia Neuropathy Spectrum/Alpers Syndrome | ANS | Multisystemic disorder | POLG | 203700 |
Ataxia-telangiectasia | AT | Multisystemic disorder | ATM | 208900 |
Biotinidase Deficiency | BTD deficiency | Metabolic disorder | BTD | 253260 |
Canavan Disease | CD | Leukodystrophy | ASPA | 271900 |
Cystic Fibrosis | CF | Multisystemic disorder | CFTR | 219700 |
Galactosemia | Galactosemia | Metabolic disorder | GALT | 230400 |
Gaucher Disease | GD | Multisystemic disorder | GBA | 230800 |
Glycine Encephalopathy | GCE | Metabolic disorder | GCSH, GLDC, AMT | 605899 |
Glycogen Storage Disease Type VI | GSD6 | Metabolic disorder | GBE1 | 232700 |
Hunter Syndrome/Mucopolysaccharidosis, Type II (MPS II) | MPS II | Metabolic disorder | IDS | 309900 |
Hypochondroplasia | HCH | Skeletal dysplasia | FGFR3 | 146000 |
Inherited Deafness | ID | Deafness | GJB2, GJB3, GJB6, COL11A2, KCNQ4 | 220290 |
Maple syrup Urine Disease | MSUD | Metabolic disorder | BCKDHA, BCKDHB, DBT, DLD | 248600 |
Marshall syndrome | MRSHS | Skeletal dysplasia | COL11A1 | 154780 |
Methylmalonic Acidemia | MMA | Metabolic disorder | MMAA, MMAB, MMACHC, MUT | 251100 |
Noonan Syndrome (Types 1, 3, 4, 5 ,6) | NS | Multisystemic disorder | KRAS, NRAS, PTPN11, RAF1, SOS1 | 163950/609942/610733/611533/613224 |
Ornithine Transcarbamylase Deficiency | OTD | Metabolic disorder | OTC | 311250 |
Phenylketonuria | PKU | Metabolic disorder | PAH | 261600 |
Pompe Disease/Glycogen Storage Disease II (GSD II) | GSDII | Metabolic disorder | GAA | 232300 |
Smith-Lemli-Optiz Syndrome | SLOS | Metabolic disorder | DHCR7 | 270400 |
Usher Syndrome Type 1 | USH1 | Deafness | PCDH15, USH1C, CDH23, MYO7A | 276900/601067 |
Very Long Chain Acyl-Coenzyme A Dehydrogenase Deficiency | ACADVLD | Metabolic disorder | ACADVL | 201475 |
Wiskott-Aldrich Syndrome | WAS | Immunodeficiency | WAS | 301000 |
X-Linked Adrenoleukodystrophy | ALD | Leukodystrophy | ABCD1 | 300100 |
Original Mutation | IDP Panel | |||||
---|---|---|---|---|---|---|
Case ID | Gene | Transcript ID | cDNA | Protein | Original Mutation Found (Y/N) | Genotype Matching (Y/N) |
13-0045 | ABCD1 | NM_000033 | c.1581C>A | p.Y527X | Y | Y |
13-0051 | ACADVL | NM_000018 | c.65C>A | p.S22X | Y | Y |
14-3258 | ACADVL | NM_000018 | c.65C>A | p.S22X | Y | Y |
13-0097 | AMT | NM_001164710 | c.533G>A | p.R178H | Y | Y |
13-0098 | AMT | NM_001164710 | c.280C>T | p.R94W | Y | Y |
13-0059 | ARSA | NM_000487 | c.1055A>G | p.N352S | Y | Y |
13-0095 | ARSA | NM_000487 | #Missense | Y | Y | |
13-0040 | ASL | NM_001024943 | c.1000C>T | p.Q334X | Y | Y |
13-0131 | ASL | NM_001024943 | c.556C>T | p.R186W | Y | Y |
13-0132 | ASL | NM_001024943 | c.544C>T | p.R182X | Y | Y |
13-0133 | ASPA | NM_000049 | #Frameshift insertion | N | NA | |
14-3064 | ASPA | NM_000049 | #Frameshift deletion | N | NA | |
13-0020 | ATM | NM_000051 | c.381_381delA | p.V128* | Y | Y |
13-0009 | BCKDHA | NM_000709 | c.905A>C | p.D302A | Y | Y |
13-0013 | BCKDHA | NM_000709 | c.905A>C | p.D302A | Y | Y |
13-0093 | BCKDHA | NM_000709 | c.1270C>T | p.Q424X | Y | Y |
13-0094 | BCKDHA | NM_000709 | c.647-1G>C | NA | Y | Y |
13-0096 | BCKDHA | NM_000709 | c.347A>G | p.D116G | Y | Y |
13-0120 | BCKDHA | NM_000709 | c.808G>A | p.A270T | Y | Y |
13-0135 | BCKDHA | NM_000709 | c.659_662delCGTA | p.Y221Qfs*108 | Y | Y |
13-0091 | BCKDHB | NM_000056 | c.286_288delGAA | p.E96del | N | NA |
13-0092 | BCKDHB | NM_000056 | c.1A>T | p.M1L | N | NA |
13-0129 | BCKDHB | NM_000056 | c.1006G>A | p.G336S | Y | Y |
13-0053 | BTD | NM_000060 | #Missense | Y | Y | |
13-0061 | BTD | NM_000060 | #Frameshift deletion | Y | Y | |
13-0062 | BTD | NM_000060 | #Missense | Y | Y | |
13-0087 | BTD | NM_000060 | #Missense | Y | Y | |
13-0088 | BTD | NM_000060 | #Frameshift deletion | Y | Y | |
13-0019 | BTK | NM_000061 | c.763C>T | p.R255X | Y | Y |
13-0028 | BTK | NM_000061 | c.982C>T | p.Q328X | Y | Y |
13-0043 | CFTR | NM_000492 | c.1418_1418delG | p.G473Efs*54 | N | NA |
13-0054 | CFTR | NM_000492 | c.1520_1522delTCT | p.F508del | Y | Y |
14-3079 | CFTR | NM_000492 | c.3700A>G | p.I1234V | Y | Y |
14-3072 | CFTR | NM_000492 | c.416A>T | p.H139L | Y | Y |
14-3071 | CFTR | NM_000492 | c.3700A>G | p.I1234V | Y | Y |
13-0090 | CDH23 | NM_001171930 | #Missense | Y | Y | |
13-0102 | COL11A1 | NM_080630 | c.2354G>A | p.G785E | Y | Y |
13-0011 | DBT | NM_001918 | c.61_61delC | p.R21Afs*12 | Y | Y |
13-0046 | DBT | NM_001918 | c.773-2A>G | NA | Y | Y |
13-0099 | DBT | NM_001918 | c.1195T>C | p.S399P | Y | Y |
13-0104 | DBT | NM_001918 | c.1281+3A>G | NA | Y | Y |
13-0107 | DBT | NM_001918 | c.137A>G | p.K46R | Y | Y |
13-0127 | DBT | NM_001918 | c.773-2A>G | NA | Y | Y |
13-0108 | DHCR7 | NM_001163817 | c.861C>G | p.N287K | Y | Y |
13-0100 | FGFR3 | NM_000142 | c.1138G>A | p.G380R | Y | Y |
13-0010 | GAA | NM_000152 | #Nonsense | Y | Y | |
13-0012 | GAA | NM_000152 | #Nonsense | Y | Y | |
13-0055 | GAA | NM_000152 | #Nonsense | Y | Y | |
13-0103 | GAA | NM_000152 | #Nonsense | Y | Y | |
13-0109 | GAA | NM_000152 | #Missense | Y | Y | |
13-0110 | GAA | NM_000152 | #Missense | Y | Y | |
13-0124 | GAA | NM_000152 | c.655G>A | p.G219R | Y | Y |
13-0128 | GAA | NM_000152 | #Nonsense | Y | Y | |
13-0064 | GALT | NM_000155 | #Frameshift deletion | Y | Y | |
13-0125 | GALT | NM_001258332 | #Missense | Y | Y | |
13-0134 | GALT | NM_001258332 | #Missense | Y | Y | |
14-3078 | GALT | NM_001258332 | #Missense | Y | Y | |
14-3067 | GALT | NM_001258332 | #Missense | Y | Y | |
13-0101 | GBA | NM_000157 | c.152G>T | p.S51I | Y | Y |
13-0130 | GBE1 | NM_000158 | #Missense | Y | Y | |
13-0116 | GJB2 | NM_004004 | c.299T>C | p.W77R | Y | Y |
13-0116 | GJB2 | NM_004004 | c.506G>A | p.C169Y | Y | Y |
13-0111 | GLDC | NM_000170 | c.2113G>A | p.V705M | Y | Y |
13-0060 | IDS | NM_000202 | #Nonsense | Y | Y | |
13-0112 | MMAA | NM_172250 | #Nonsense | Y | Y | |
13-0126 | MMAA | NM_172250 | #Missense | Y | Y | |
13-0063 | MUT | NM_000255 | #Frameshift deletion | Y | Y | |
13-0105 | MUT | NM_000255 | c.329A>G | p.Y110C | Y | Y |
13-0121 | MUT | NM_000255 | c.278G>A | p.R93H | Y | Y |
14-3081 | MUT | NM_000255 | c.1160C>T | p.T387I | Y | Y |
14-3080 | MUT | NM_000255 | c.2200C>T | p.Q734X | Y | Y |
14-3070 | MUT | NM_000255 | c.2200C>T | p.Q734X | Y | Y |
14-3065 | MUT | NM_000255 | c.1677-1G>C | NA | Y | Y |
13-0044 | MYO7A | NM_000260 | c.5880-5882delCTT | p.F1961del | Y | Y |
13-0117 | MYO7A | NM_000260 | c.2005C>T | p.R669X | Y | Y |
13-0066 | OTC | NM_000531 | #Missense | Y | Y | |
13-0057 | PAH | NM_000277 | #Missense | Y | Y | |
13-0113 | PAH | NM_000277 | #Nonsense | Y | Y | |
13-0114 | PAH | NM_000277 | #Missense | N | NA | |
13-0122 | PAH | NM_000277 | #Missense | Y | Y | |
13-0123 | PAH | NM_000277 | #Nonsense | Y | Y | |
13-0136 | PAH | NM_000277 | #Missense | Y | Y | |
14-3073 | PAH | NM_000277 | #Missense | Y | Y | |
13-0058 | POLG | NM_001126131 | c.2419C>T | p.R807C | Y | Y |
13-0115 | PTPN11 | NM_002834 | c.188A>G | p.Y63C | Y | Y |
13-0026 | WAS | NM_000377 | c.91G>A | p.E31K | Y | Y |
13-0027 | WAS | NM_000377 | c.100C>T | p.R34X | Y | Y |
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Mustafa, A.E.; Faquih, T.; Baz, B.; Kattan, R.; Al-Issa, A.; Tahir, A.I.; Imtiaz, F.; Ramzan, K.; Al-Sayed, M.; Alowain, M.; et al. Validation of Ion TorrentTM Inherited Disease Panel with the PGMTM Sequencing Platform for Rapid and Comprehensive Mutation Detection. Genes 2018, 9, 267. https://doi.org/10.3390/genes9050267
Mustafa AE, Faquih T, Baz B, Kattan R, Al-Issa A, Tahir AI, Imtiaz F, Ramzan K, Al-Sayed M, Alowain M, et al. Validation of Ion TorrentTM Inherited Disease Panel with the PGMTM Sequencing Platform for Rapid and Comprehensive Mutation Detection. Genes. 2018; 9(5):267. https://doi.org/10.3390/genes9050267
Chicago/Turabian StyleMustafa, Abeer E., Tariq Faquih, Batoul Baz, Rana Kattan, Abdulelah Al-Issa, Asma I. Tahir, Faiqa Imtiaz, Khushnooda Ramzan, Moeenaldeen Al-Sayed, Mohammed Alowain, and et al. 2018. "Validation of Ion TorrentTM Inherited Disease Panel with the PGMTM Sequencing Platform for Rapid and Comprehensive Mutation Detection" Genes 9, no. 5: 267. https://doi.org/10.3390/genes9050267