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 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 + 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 Aortopathy panel See Marfan syndrome Any one of the above Full mutation by Sanger sequencing (+ MLPA for SOX2 only) Page 1 of 11
Beckwith-Wiedemann syndrome Chromosome 11 abnormalities 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 FOXL2 Full mutation + MLPA inversus syndrome) Breast/ovarian cancer Full s 545 BRCA1, BRCA2 Next-generation sequencing + MLPA NGS service Ashkenazi Jewish founder mutations: Ovarian cancer Charcot-Marie-Tooth disease type 1A Dosage only Full Charcot-Marie-Tooth disease type 1B Charcot-Marie-Tooth disease, X-linked Charcot-Marie-Tooth disease, other Chronic myeloid leukaemia (CML) Chronic lymphoblastic leukaemia (CLL) 515 BRCA1, BRCA2 RAD51C, RAD51D PMP22 PMP22 MPZ GJB1 (CX32) POA Further CMT genes available on request See Haematological malignancies See Haematological malignancies 3 specific mutations by highthroughput Next-generation sequencing Duplication by MLPA and MLPA Full mutation + MLPA Full mutation + MLPA NGS service Single or multiple gene Page 2 of 11
Cowden syndrome Full PTEN Mutation ing by nextgeneration sequencing + MLPA NGS service PTEN promoter mutation Cystic fibrosis Routine diagnostic or carrier testing Urgent carrier testing 205 750 750 900 14 112 112 112 PTEN CFTR CFTR of promoter 50 of the most common mutations 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 NGS service 13-gene panel genes included on these panels 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 (One common mutation) Duchenne/Becker muscular dystrophy 205 DMD MLPA Factor V Leiden & Prothrombin mutations 205 F5, F2 Page 3 of 11
Familial ing Family testing (carrier, parental, segregation) 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) 14 FMR1 FMR1 AFF2 AFF2 See Amyotrophic lateral sclerosis 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 + 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 110 320 110 for all 4 tests 175 14 SETBP1, CSF3R Up to 54 genes (full s or hotspots) CALR, MPL JAK2 JAK2 FIP1L1-PDGFRA fusion (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 110 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 PMP22 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 Paternal UPD(14) follow-up, see UPD studies Kallman syndrome Autosomal X-linked Léri Weill dyschondrosteosis (LWD) Dosage only Full 205 HTT See Cystic fibrosis and Y microdeletion 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 505 505 405 FGFR1 ANOS1 (KAL1) SHOX SHOX + MLPA + 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 NGS service Microsatellite instability (MSI) 275 Analysis of 5 microsatellite loci on paired blood DNA + tumour DNA (>3 stable = MS-Stable; >1 unstable = Specialised testing Page 6 of 11
Lynch syndrome (HNPCC) contd MSI-High) BRAF V600E status BRAF Marfan syndrome Full (not including MLPA) 750-950 or 112 6-or 19-gene panel MLPA (on request only) Microphthalmia 200 See Anophthalmia FBN1, TGFBR1, TGFBR2 See separate NGS service list for details of genes included MLPA NGS service Multiple gene Mental retardation, autosomal dominant 31 (OMIM#616158) PURA Mowat-Wilson syndrome 750 ZEB2 Full mutation + MLPA Multiple exostoses/multiple osteochondromas 670 EXT1, EXT2 Next-generation sequencing + MLPA NGS service MUTYH-associated polyposis 205 MUTYH for two common mutations Myeloproliferative neoplasia (MPN) See Haematological malignancies Myotonic dystrophy type 1 PCR only Southern blot 205 500 DMPK DMPK Fluorescent PCR/TP-PCR Two Southern blots (Normal: 5-36 repeats; Intermediate: 37-50 repeats; Affected: >50 repeats) Myotonic dystrophy type 2 205 CNBP (PROMM) Fluorescent PCR/TP-PCR (Normal range: up to 26 repeats) Neurofibromatosis (NF1) and 675 NF1, SPRED1 Next-generation sequencing + MLPA NGS service Neurofibromatosis-Like Syndrome Noonan syndrome NGS service 14-gene panel 750 112 See NGS service list Next-generation sequencing Page 7 of 11
Noonan syndrome (contd) 14-gene panel (data only) 300 112 See NGS service list Next-generation sequencing (data) NGS service 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 MLPA Progressive myoclonic epilepsy of Unverricht and Lundborg (EPM1) Dodecamer repeat expansion Point mutation Pseudohypoparathyroidism type 1b (PHP1b) GNAS abnormalities PABPN1 PABPN1 Fluorescent PCR (Normal: 10 repeats; Pathogenic: 11-17 repeats) 205 Methylation-sensitive MLPA - 0-0 205 205 3 3 CSTB CSTB + QF-PCR for maternal cell contamination testing MLPA + QF-PCR for maternal cell contamination testing DNA deamination + PCR (Normal: 2 or 3 repeats; Affected: >29 repeats) 205 GNAS MS-MLPA UPD(20) follow-up, see UPD studies Rett syndrome 350 MECP2 Full mutation + MLPA Page 8 of 11
Rett syndrome (congenital variant) 225 FOXG1 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 CREBBP 750 CREBBP Sequencing + MLPA EP300 Russell-Silver syndrome Sequencing of known mutations Confirmations Family or predictive testing 750 See Silver-Russell syndrome or 14 EP300 Sequencing + MLPA 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 and MLPA Dosage only Silver-Russell syndrome Chromosome 11 abnormalities UPD(7) follow-up by MLPA 205 Methylation-specific MLPA Smith-Magenis syndrome 750 RAI1 Full mutation + MLPA Sorsby fundus dystrophy TIMP3 Sequencing of mutation hotpsots SHOX ICR1 only MLPA MS-MLPA /MS-PCR Page 9 of 11
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 See Marfan syndrome STS STS MLPA dosage 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 UPD studies (any chromosome) First-line test Follow-up test (e.g. of imprinting abnormality) 505 300 FGFR3 Sequencing of mutation hotspots Microsatellite (parental samples required) Microsatellite (parental samples required) Page 10 of 11
Validation or confirmation of single mutation Existing test (sequence mutations) Existing test (copy number mutations) MLPA Development of new test 300 Amplicon design and Sanger sequencing Von Hippel-Lindau 360 VHL Next-generation sequencing + MLPA NGS service 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