Achondroplasia + Hypochondroplasia FGFR3 Common mutations in FGFR3 (1138 G>A/C and 1620C>A/G)

Transcription

1 DISEASE / DISORDER Price Routine TAT (Calendar Days) Gene(s) or locus Description of test (including reference intervals/ clinical decision values where applicable) Category Achondroplasia + Hypochondroplasia FGFR3 Common mutations in FGFR3 (1138 G>A/C and 1620C>A/G) Adrenal hypoplasia, congenital X-linked 605 NR0B1 (DAX1) Full mutation + MLPA Albinism and nystagmus gene panel See separate list for details of genes included Alpha 1 - antitrypsin deficiency SERPINA1 2 common mutations (S& Z) Amyloidosis (Finnish type) GSN Specific mutation Amyotrophic lateral sclerosis (ALS) / Frontal temporal dementia (FTD) Angelman syndrome Chromosome 15 abnormalities C9orf72 Hexanucleotide repeat expansion : PCR + RP-PCR (Normal: 2-20 repeats; Pathogenic: > repeats; Reduced penetrance: - approx. 300 repeats) MS-PCR / MS-MLPA UPD(15) follow-up, see UPD studies Aniridia 605 PAX6 Next-generation sequencing + MLPA Anophthalmia + Microphthalmia 4-gene panel 5-gene panel SOX2, BMP4, OTX2, RAX SOX2, BMP4, OTX2, RAX, PITX2 Full mutation by Sanger sequencing (+ MLPA for SOX2 only) Full mutation by Sanger sequencing (+ MLPA for SOX2 only) Multiple gene Multiple gene Individual gene Any one of the above Full mutation by Sanger sequencing (+ MLPA for SOX2 only) Page 1 of 11

2 Aortopathy panel Beckwith-Wiedemann syndrome Chromosome 11 abnormalities See Marfan syndrome ICR1 and ICR2 MS-PCR / MS-MLPA UPD(11) follow-up, see UPD studies BOFS (Brachio-ocular facial syndrome) 500 TFAP2A Full mutation by Sanger sequencing BPES (blepharophimosis, ptosis, and epicanthus 400 FOXL2 Full mutation + MLPA inversus syndrome) Breast/ovarian cancer Full s 545 BRCA1, BRCA2 Next-generation sequencing + MLPA Ashkenazi Jewish founder mutations: Ovarian cancer Charcot-Marie-Tooth disease type 1A Dosage only Please note that from May 1st 2018, WRGL will only be offering duplication ; all full gene s will be discontinued and outsourced as part of the national reconfiguration of genetics services. Please contact the laboratory if you would like further details. Chronic myeloid leukaemia (CML) Chronic lymphoblastic leukaemia (CLL) Cowden syndrome Full 565 BRCA1, BRCA2 RAD51C, RAD51D 3 specific mutations by highthroughput Sanger sequencing Next-generation sequencing + MLPA PMP22 Duplication by MLPA See Haematological malignancies See Haematological malignancies 400 PTEN Mutation ing by nextgeneration sequencing + MLPA PTEN promoter mutation PTEN Sanger sequencing of promoter Page 2 of 11

3 Cystic fibrosis Routine diagnostic or carrier testing 180 CFTR 50 of the most common mutations Urgent carrier testing CFTR 50 of the most common mutations Newborn from blood spots (working days) CFTR 4 most common mutations in the UK Di George syndrome MLPA for 22q11 deletions Disorders of sexual development (DSD) Gender assignment See separate list for 13-gene panel details of genes included Genital anomalies and suspected adrenal problems 12-gene panel Gonadal dysgenesis with gonadal failure 12-gene panel DSD 28-gene panel Doyne honeycomb retinal dystrophy EFEMP1 Sanger sequencing (One common mutation) Duchenne/Becker muscular dystrophy DMD MLPA Early infantile epileptic encephalopathy gene panel See separate list for details of genes included Factor V Leiden & Prothrombin mutations F5, F2 Page 3 of 11

4 Familial ing Family testing (carrier, parental, segregation) 180 Sanger sequencing or MLPA (requires positive control) Predictive testing Sanger sequencing or MLPA (requires positive control) Fragile X syndrome (FRAXA) FRAXA PCR only FMR1 Fluorescent long-template PCR (Normal: up to 45 repeats; Intermediate: repeats; Premutation: repeats; Full mutation: >200 repeats) Frontal temporal dementia (FTD) See Amyotrophic lateral sclerosis Glaucoma MYOC Mutation ing Haematological malignancies AML core binding factor AML 3-gene panel FLT3 ITD, FLT3 TKD and NPM1 FLT3 ITD and FLT3 TKD FLT3 ITD FLT3 TKD NPM1 IDH1 and IDH2 IDH1 IDH KIT FLT3, NPM1 FLT3 FLT3 FLT3 NPM1 IDH1, IDH2 IDH1 IDH1 Screening of mutation hotspots by Haematooncology Chronic lymphocytic leukaemia (CLL) 280 TP53 Page 4 of 11

5 Chronic myeloid leukaemia (CML) Variant BCR-ABL1 translocations BCR-ABL1 fusion RNA/cDNA prep + fragment Chronic myeloid leukaemia (CML) BCR-ABL1 kinase domain mutations BCR-ABL1 fusion RNA/cDNA prep + Sanger sequencing of kinase domain Atypical CML, Chronic neutrophilic leukaemia Leukaemia translocations (AML, ALL) Myeloid NGS panel Myeloproliferative neoplasia (MPN) CALR (exon 9) and MPL (codons 505, 515) JAK2 V617F JAK2 exon 12 Hypereosinophilic syndrome FIP1L1-PDGFRA MRD Systemic mastocytosis (SM) KIT D816V Extended for all 4 tests N/A SETBP1, CSF3R Up to 54 genes (full s or hotspots) CALR, MPL JAK2 JAK2 FIP1L1-PDGFRA fusion KIT KIT Sanger sequencing (specific exons) Multiple RT-PCR for 29 translocation mutations See Molecular leukaemia research tests on Oncology page of website Multiplex genomic DNA PCR, nested RT-PCR Droplet digital PCR Screening of mutation hotspots by Haemochromatosis HFE 2 common mutations Page 5 of 11

6 Hereditary neuropathy with liability to pressure palsies (HNPP) Dosage only Please note that from May 1st 2018, WRGL will only be offering deletion ; all full gene s will be discontinued and outsourced as part of the national reconfiguration of genetics services. Please contact the laboratory if you would like further details. Hereditary non-polyposis colon cancer (HNPCC) See Lynch syndrome Huntington disease (HD) PCR only PCR + TP-PCR Predictive testing Infertility Kagami-Ogata syndrome Methylation abnormalities PMP22 Deletion by MLPA or 14 HTT HTT HTT See Cystic fibrosis and Y microdeletion Paternal UPD(14) follow-up, see UPD studies Kallman syndrome 5-gene panel 750 ANOS1 (KAL1), FGFR1, FGF8, PROK2, PROKR2 Fluorescent PCR Fluorescent PCR + TP-PCR (Fluorescent PCR or PCR + TP-PCR) (Normal: 8-26 repeats; Intermediate: repeats; Reduced penetrance: repeats; Pathogenic: >39 repeats) DLK1/GTL2 Methylation-sensitive MLPA Next-generation sequencing + MLPA Page 6 of 11

7 Léri Weill dyschondrosteosis (LWD) Dosage only SHOX MLPA only Full 405 SHOX Full mutation including MLPA Linkage (up to 4 patients) 505 Microsatellite Specialised testing Lynch syndrome (HNPCC) Full BRAF V600E status Microsatellite instability (MSI) Marfan syndrome Full (not including MLPA) MLPA (on request only) Microphthalmia or 84 See Anophthalmia MLH, MSH2, MSH6 BRAF 6-or 19-gene panel FBN1, TGFBR1, TGFBR2 Next-generation sequencing + MLPA Analysis of 5 microsatellite loci on paired blood DNA + tumour DNA (>3 stable = MS-Stable; >1 unstable = MSI-High) See separate list for details of genes included MLPA Specialised testing Multiple gene Mental retardation, autosomal dominant PURA Sanger sequencing (OMIM#616158) Mowat-Wilson syndrome 750 ZEB2 Next-generation sequencing + MLPA Multiple exostoses/multiple osteochondromas 670 EXT1, EXT2 Next-generation sequencing + MLPA MUTYH-associated polyposis MUTYH for two common mutations Page 7 of 11

8 Myeloproliferative neoplasia (MPN) Myotonic dystrophy Myotonic dystrophy type 1 Myotonic dystrophy type 2 Neurofibromatosis (NF1) and Neurofibromatosis-Like syndrome Noonan syndrome 14-gene panel 14-gene panel (data only) Oculopharyngeal muscular dystrophy (OPMD) Triplet repeat Test for single point mutation c.35g>c Prader-Willi syndrome Chromosome 15 abnormalities UPD(15) follow-up, see UPD studies Prenatal testing of known mutations Sanger sequencing See Haematological malignancies DMPK Fluorescent PCR/TP-PCR (Normal: 5-36 repeats; Intermediate: repeats; Affected: >50 repeats) CNBP (PROMM) Fluorescent PCR/TP-PCR (Normal range: up to 26 repeats) 675 NF1, SPRED1 Next-generation sequencing + MLPA See list See list PABPN1 PABPN1 Next-generation sequencing Next-generation sequencing (data) Fluorescent PCR (Normal: 10 repeats; Pathogenic: repeats) Sanger sequencing Methylation-sensitive MLPA Sanger sequencing + QF-PCR for maternal cell contamination testing MLPA MLPA + QF-PCR for maternal cell contamination testing Primary ciliary dyskinesia gene panel See separate list for details of genes included Page 8 of 11

9 Progressive myoclonic epilepsy of Unverricht and Lundborg (EPM1) Dodecamer repeat expansion CSTB DNA deamination + PCR (Normal: 2 or 3 repeats; Affected: >29 repeats) Point mutation Pseudohypoparathyroidism type 1b (PHP1b) GNAS abnormalities UPD(20) follow-up, see UPD studies Rett syndrome CSTB Sanger sequencing GNAS MS-MLPA 350 MECP2 Full mutation + MLPA Rett syndrome (congenital variant) 225 FOXG1 Full mutation + MLPA RNA studies (investigating the effect of 520 Analysis of DNA variants for splicing Specialised sequence variants on splicing) abnormalities testing Rubinstein-Taybi syndrome 2-gene panel 750 CREBBP, EP300 Next-generation sequencing + MLPA Russell-Silver syndrome Sequencing of known mutations Confirmations Family or predictive testing See Silver-Russell syndrome 180 or 14 Sequencing of index case only Sequencing of index case and control Setting up new test 300 N/A Primer design and optimisation Sequencing of index case only Sexing of CV samples for molecular QF-PCR Specialised testing Page 9 of 11

10 Short stature Full 405 SHOX Sanger sequencing and MLPA Dosage only Silver-Russell syndrome Chromosome 11 abnormalities UPD(7) follow-up by MLPA Methylation-specific MLPA Smith-Magenis syndrome 750 RAI1 Next-generation sequencing + MLPA SHOX ICR1 only MLPA MS-MLPA /MS-PCR Sorsby fundus dystrophy 180 TIMP3 Sequencing of mutation hotspots Spinal muscular atrophy, SMA (5q13-linked) SMN1 MLPA dosage Steroid sulphatase deficiency (X-linked ichthyosis) Dosage only for common microdeletion Point ing TAAD (Thoracic Aortic Aneurism Dissection) Temple syndrome Methylation abnormalities 400 See Marfan syndrome STS STS MLPA dosage Next-generation sequencing NOTE: Dosage and point mutation performed separately (as 90% of pathogenic STS mutations are whole gene deletions) DLK1/GTL2 Methylation-sensitive MLPA Maternal UPD(14) follow-up, see UPD studies Thanataphoric dysplasia 300 FGFR3 Sequencing of mutation hotspots Page 10 of 11

11 Transient neonatal diabetes mellitus (TNDM) 6q24 methylation, UPD and dosage by MLPA Unverricht-Lundborg disease See Progressive myoclonic epilepsy UPD studies (any chromosome) First-line test Follow-up test (e.g. of imprinting abnormality) Validation or confirmation of single mutation Existing test (sequence mutations) Existing test (copy number mutations) Development of new test Variant re-interpretation Simple report Microsatellite (parental samples required) Microsatellite (parental samples required) Sanger sequencing MLPA Amplicon design and Sanger sequencing Interpretation of variants previously reported as uncertain significance Interpretation only Complex report with full re-interpretation Witkop syndrome 405 MSX1 Full mutation X-inactivation studies (e.g. X-linked inheritance, Methylation by restriction Specialised CNV or VUS assessment) enzyme digestion testing (Random = <80:20 ratio; skewed = >91:9 ratio). X-linked ichthyosis See Steroid sulphatase deficiency Y microdeletions (AZFa, b, and c) MLPA Page 11 of 11