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 205 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 800 112 31-gene panel See www.ukgtn.nhs.uk for details of genes included on these panels Alpha 1 - antitrypsin deficiency 205 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 205 C9orf72 Hexanucleotide repeat expansion : PCR + RP-PCR (Normal: 2-20 repeats; Pathogenic: > repeats; Reduced penetrance: - approx. 300 repeats) 205 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 750 900 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
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 1 st 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 515 BRCA1, BRCA2 RAD51C, RAD51D 3 specific mutations by highthroughput Sanger sequencing Next-generation sequencing PMP22 Duplication by MLPA See Haematological malignancies See Haematological malignancies 400 PTEN Mutation ing by nextgeneration sequencing + MLPA PTEN promoter mutation 205 PTEN Sanger sequencing of promoter Page 2 of 11
Cystic fibrosis Routine diagnostic or carrier testing CFTR 50 of the most common mutations Urgent carrier testing 14 CFTR 50 of the most common mutations Newborn from blood spots 110 4 CFTR 4 most common mutations in the UK Di George syndrome MLPA for 22q11 deletions Disorders of sexual development (DSD) 750 112 Gender assignment See www.ukgtn.nhs.uk for details of 13-gene panel genes included on these panels 750 750 900 112 112 112 Genital anomalies and suspected adrenal problems 12-gene panel Gonadal dysgenesis with gonadal failure 12-gene panel DSD -gene panel Doyne honeycomb retinal dystrophy EFEMP1 Sanger sequencing (One common mutation) Duchenne/Becker muscular dystrophy 205 DMD MLPA Early infantile epileptic encephalopathy 750 112 78-gene panel See separate list for details of genes included Factor V Leiden & Prothrombin mutations 205 F5, F2 Page 3 of 11
Familial ing Family testing (carrier, parental, segregation) Sanger sequencing or MLPA (requires positive control) Predictive testing Fragile X syndrome (FRAXA or FRAXE) FRAXA PCR only FRAXA Southern blot FRAXE PCR only FRAXE Southern blot Frontal temporal dementia (FTD) 400 400 14 FMR1 FMR1 AFF2 AFF2 See Amyotrophic lateral sclerosis Sanger sequencing or MLPA (requires positive control) Fluorescent long-template PCR Southern blot (Normal: up to 45 repeats; Intermediate: 46-58 repeats; Premutation: 59-200 repeats; Full mutation: >200 repeats) Fluorescent long-template PCR Southern blot (Normal: up to 30 repeats; Intermediate: 31-60 repeats; Premutation: 61-200 repeats; Full mutation: >200 repeats) Glaucoma MYOC Mutation ing Haematological malignancies AML core binding factor Chronic lymphocytic leukaemia (CLL) 0 0 N/A N/A KIT TP53 Screening of mutation hotspots by Haematooncology Chronic myeloid leukaemia (CML) Variant BCR-ABL1 translocations BCR-ABL1 fusion RNA/cDNA prep + fragment Page 4 of 11
Haematological malignancies (contd) 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 120 340 120 for all 4 tests 120 14 SETBP1, CSF3R Up to 54 genes (full s or hotspots) CALR, MPL JAK2 JAK2 FIP1L1-PDGFRA fusion 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 Systemic mastocytosis (SM) KIT D816V Extended 120 0 N/A KIT KIT Droplet digital PCR Screening of mutation hotspots by Haemochromatosis 205 HFE 2 common mutations Hereditary neuropathy with liability to pressure palsies (HNPP) Dosage PMP22 Deletion by MLPA Full 400 PMP22 Sanger sequencing and MLPA Page 5 of 11
Hereditary non-polyposis colon cancer (HNPCC) See Lynch syndrome Huntington disease (HD) PCR only HTT Fluorescent PCR PCR + TP-PCR Infertility Kagami-Ogata syndrome Methylation abnormalities 205 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 Léri Weill dyschondrosteosis (LWD) Dosage only SHOX Full Fluorescent PCR + TP-PCR (Normal: 8-26 repeats; Intermediate: 27-35 repeats; Reduced penetrance: 36-39 repeats; Pathogenic: >39 repeats) 205 DLK1/GTL2 Methylation-sensitive MLPA 405 SHOX Next-generation sequencing + MLPA MLPA only Full mutation including MLPA Linkage (up to 4 patients) 505 Microsatellite Specialised testing Lynch syndrome (HNPCC) Full 500 MLH, MSH2, MSH6 Next-generation sequencing + MLPA BRAF V600E status BRAF Specialised testing Page 6 of 11
Lynch syndrome (HNPCC) contd Microsatellite instability (MSI) 275 Analysis of 5 microsatellite loci on paired blood DNA + tumour DNA (>3 stable = MS-Stable; >1 unstable = MSI-High) Marfan syndrome Full (not including MLPA) MLPA (on request only) Microphthalmia 750-950 200 or 112 See Anophthalmia 6-or 19-gene panel FBN1, TGFBR1, TGFBR2 See separate list for details of genes included MLPA Multiple gene Mental retardation, autosomal dominant 31 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 205 MUTYH for two common mutations Myeloproliferative neoplasia (MPN) See Haematological malignancies Myotonic dystrophy Myotonic dystrophy type 1 205 DMPK Fluorescent PCR/TP-PCR (Normal: 5-36 repeats; Intermediate: 37-50 repeats; Affected: >50 repeats) Myotonic dystrophy type 2 Neurofibromatosis (NF1) and Neurofibromatosis-Like Syndrome 205 CNBP (PROMM) Fluorescent PCR/TP-PCR (Normal range: up to 26 repeats) 675 NF1, SPRED1 Next-generation sequencing + MLPA Page 7 of 11
Noonan syndrome 14-gene panel 750 112 See list Next-generation sequencing 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 300 112 See list PABPN1 PABPN1 Next-generation sequencing (data) Fluorescent PCR (Normal: 10 repeats; Pathogenic: 11-17 repeats) Sanger sequencing 205 Methylation-sensitive MLPA - 0 3 Sanger sequencing + QF-PCR for maternal cell contamination testing MLPA - 0 3 MLPA + QF-PCR for maternal cell contamination testing Primary ciliary dyskinesia 800 112 29-gene panel See separate list for details of genes included Progressive myoclonic epilepsy of Unverricht and Lundborg (EPM1) Dodecamer repeat expansion Point mutation 205 205 CSTB CSTB DNA deamination + PCR (Normal: 2 or 3 repeats; Affected: >29 repeats) Sanger sequencing Page 8 of 11
Pseudohypoparathyroidism type 1b (PHP1b) GNAS abnormalities 205 GNAS MS-MLPA UPD(20) follow-up, see UPD studies Rett syndrome Rett syndrome (congenital variant) 350 225 MECP2 FOXG1 Full mutation + MLPA Full mutation + MLPA RNA studies (investigating the effect of sequence variants on splicing) 520 Analysis of DNA variants for splicing abnormalities Specialised 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 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 3 QF-PCR Specialised testing Short stature Full 405 SHOX Sanger sequencing and MLPA Dosage only Silver-Russell syndrome Chromosome 11 abnormalities SHOX ICR1 only MLPA MS-MLPA /MS-PCR UPD(7) follow-up by MLPA 205 Methylation-specific MLPA Smith-Magenis syndrome 750 RAI1 Next-generation sequencing + MLPA Page 9 of 11
Sorsby fundus dystrophy TIMP3 Sequencing of mutation hotpsots 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 Maternal UPD(14) follow-up, see UPD studies Thanataphoric dwarfism Type 1 400 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) 205 DLK1/GTL2 Methylation-sensitive MLPA Type 2 FGFR3 Sequencing of mutation hotspot Transient neonatal diabetes mellitus (TNDM) 205 6q24 methylation, UPD and dosage by MLPA Unverricht-Lundborg disease See Progressive myoclonic epilepsy FGFR3 Sequencing of mutation hotspots Page 10 of 11
UPD studies (any chromosome) First-line test 505 Microsatellite (parental samples required) Follow-up test (e.g. of imprinting abnormality) Validation or confirmation of single mutation Existing test (sequence mutations) Existing test (copy number mutations) 300 Microsatellite (parental samples required) Sanger sequencing Development of new test 300 Amplicon design and Sanger sequencing Von Hippel-Lindau 360 VHL Next-generation sequencing + MLPA MLPA Witkop syndrome 405 MSX1 Full mutation X-inactivation studies (e.g. X-linked inheritance, CNV or VUS assessment) 205 Methylation by restriction enzyme digestion (Random = <80:20 ratio; skewed = >91:9 ratio). Specialised testing X-linked ichthyosis See Steroid sulphatase deficiency Y microdeletions (AZFa, b, and c) MLPA Page 11 of 11