The schedule for the lab’s tests accredited by UKAS can be found at: UKAS 8413 schedule.
RAS-MAPK pathway gene sequencing
Genes of the RAS-MAPK pathway are important for growth-factor mediated cell proliferation, differentiation and survival. Variants in genes of this pathway are responsible for a number of developmental syndromes: Noonan syndrome, LEOPARD syndrome, Costello syndrome and cardio-facio-cutaneous (CFC) syndrome. This test provides sequencing of 100% of the coding regions and flanking intronic sequences of 18 genes of the RAS-MAPK pathway: BRAF, CBL, HRAS, KRAS, LZTR1, MAP2K1, MAP2K2, NF1, MRAS, NF1, NRAS, PPP1CB, PTP11, RAF1, RIT1, SHOC2, SOS1 and SPRED1.
For more details please read the RAS-MAPK pathway gene sequencing information sheet (PDF format)
Familial Hypertrophic Cardiomyopathy (HCM) gene sequencing
Hypertrophic cardiomyopathy (HCM) is characterised by unexplained left ventricular hypertrophy (LVH) that develops in the absence of predisposing cardiac or cardiovascular conditions. It has an estimated prevalence of 1 in 500 worldwide, making it the most common inherited cardiomyopathy. HCM can be caused by variants in genes encoding protein components of the cardiac muscle sarcomere. This test provides sequencing of 100% of the coding regions and flanking intronic sequences of 19 genes implicated in development of HCM: ACTC1, ACTN2, CSRP3, FHL1, FLNC, GLA, JPH2, LAMP2, MYBPC3, MYH7, MYL2, MYL3, PLN, PRKAG2, TNNC1, TNNI3, TNNT2, TPM1 and TTR
For more details please read the Familial hypertrophic cardiomyopathy gene sequencing information sheet (PDF format)
Familial Dilated Cardiomyopathy (DCM) gene sequencing
Hereditary dilated cardiomyopathy (DCM) is characterised by unexplained left ventricular enlargement and systolic dysfunction, with a reduction in the myocardial force of contraction. DCM, like HCM, can also be caused by variants in cardiac sarcomere genes, including several of same genes. This test provides sequencing of 100% of the coding regions and flanking intronic sequences of 25 genes implicated in the development of DCM: ACTC1, ACTN2, BAG3, CSRP3, DES, DMD, DSP, FLNC, LAMP2, LMNA, MYBPC3, MYH7, MYL2, MYL3, NKX2-5, PLN, RBM20, SCN5A, TNNC1, TNNI3, TNNI3K, TNNT2, TPM1, TTN (N2-B major cardiac muscle isoform) and VCL.
For more details please read the Familial Dilated Cardiomyopathy gene sequencing information sheet (PDF format)
Hereditary Colorectal, Breast and Ovarian cancer gene sequencing
The hereditary colorectal, breast and ovarian cancer gene panel provides sequencing for genes involved in inherited predisposition to these cancers.
- The colorectal cancer subpanel includes: APC, BMPR1A, MBD4, MLH1, MSH2, MSH3, MSH6, MUTYH, NTHL1, PMS2, POLD1 (exons 4-12), POLE (exons 3-13), PTEN, RNF43, SMAD4, STK11
- The breast subpanel includes: ATM, BRCA1, BRCA2, CHEK2, PALB2, PTEN, STK11, TP53
- The ovarian subpanel includes: BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, RAD51C, RAD51D
The CDH1 gene and DICER1 gene are also included on the panel. Analysis of these genes can be undertaken if specifically requested.
Dosage analysis will be conducted for genes relevant to the referral indication. Please see the testing pro forma for more details.
Pro forma for hereditary colorectal, breast, and ovarian testing.
For more details, please see the Hereditary Colorectal, Breast and Ovarian panel technical information sheet (PDF format).
Alport Syndrome gene sequencing
Alport syndrome is the second most common inherited cause of kidney failure. It is caused by defects in the type IV collagen, an important component of the kidney glomerular basement membrane (GBM). Patients commonly experience persistent hematuria, proteinuria, progressive renal failure, hearing loss and ocular defects. This test provides sequencing of the COL4A3, COL4A4 and COL4A5 genes, which are associated with autosomal recessive and X-linked Alport syndrome and autosomal dominant thin basement membrane nephropathy (TBMN). In addition, this test provides sequencing of the COL4A1 and MYH9 genes as pathogenic variants in these genes may cause an overlapping phenotype i.e. TBMN, hematuria, proteinuria and hearing loss (Gale et al. Nephrol Dial Transplant 2016; 31(11): 1908-1914; Savige J. Nephrol Dial Transplant 2016; 31(11): 1758-1760; Seri et al. Medicine (Baltimore) 2003; 82(3): 203-215). This test provides sequencing of 100% of the coding regions and flanking intronic sequences of the COL4A1, COL4A3, COL4A4, COL4A5 and MYH9 genes, as well as, a number of deep intronic regions encompassing previously reported pathogenic/likely pathogenic variants in COL4A4 and COL4A5.
For more details please read the Alport Syndrome gene panel technical information sheet (PDF format)
Sequencing of genes associated with Neurodegeneration
Referrals to adult neurology clinics include several diseases such as frontotemporal dementia, amyotrophic lateral sclerosis and Alzheimer disease, for which the underlying mechanism is neurodegeneration. Variants in a number of genes have been shown to cause this group of neurological diseases. This test provides sequencing of >95% of the coding regions and flanking intronic sequences of 27 genes associated with neurodegeneration: ALS2, ANG, ANXA11, APP, CHCHD10, CHMP2B, CSF1R, DCTN1, FIG4, FUS, GRN, ITM2B, MAPT, NEK1, OPTN, PFN1, PRNP, PSEN1, PSEN2, SETX, SOD1, SQSTM1, TARDBP, TBK1, UBQLN2, VAPB and VCP
For more details please read the Neurodegeneration gene sequencing information sheet (PDF Format)
Hereditary Haemorrhagic Telangiectasia gene sequencing
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterised by multi-organ vascular dysplasia. Clinical diagnosis is established with three or more of the following clinical features: epistaxis, mucocutaneous telangiectasias and visceral arteriovenous malformations (AVMs) and/or family history of HHT. Pathogenic variants in the ACVRL1, ENG, GDF2 and SMAD4 genes cause HHT with the majority detected in the ACVRL1 and ENG genes. Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is associated with pathogenic variants in the EPHB4 and RASA1 genes and has some phenotypic overlap with HHT. This test provides sequencing of 100% of the coding and flanking intronic regions of the ACVRL1, ENG, EPHB4, GDF2, RASA1 and SMAD4 genes, as well as, part of the ENG promoter and 3ʹ UTR encompassing previously reported pathogenic/likely pathogenic variants.
For more details please read the HHT gene panel technical information sheet (PDF format)
Primary Pulmonary Hypertension gene sequencing
Primary pulmonary hypertension (PPH; or primary arterial hypertension, PAH) is a progressive vascular lung disease characterised by increased vascular resistance and arterial pressure, leading to weakening of the heart and eventual heart failure. This test provides sequencing of 100% of the coding and flanking intronic regions of 11 genes associated with PPH: ACVRL1, ATP13A3, BMPR2, CAV1, GDF2, EIF2AK4, ENG, KCNK3, SMAD9, SOX17 and TBX4.
For more details please read the PPH gene panel technical information sheet (PDF format)
Ocular Malformations gene sequencing
Anophthalmia, microphthalmia, coloboma (MAC) and aniridia are severe eye malformations with a total birth incidence of >1 in 5,000. The genetic cause is identifiable in approximately 70% of severe bilateral anophthalmia or severe microphthalmia, 20-30% of bilateral coloboma with or without microphthalmia, and 90% of aniridia.
This test provides sequencing of >99% of coding regions and flanking intronic sequences for 41 genes associated with syndromal and non-syndromal MAC, and aniridia. Genes tested: ACTB, ACTG1, ALDH1A3, BCOR, C12ORF57, CHD7, COL4A1, FOXC1, FOXE3, FZD5, GJA8, ITPA, ITPR1, MAB21L1, MAB21L2, NAA10, OTX2, PAX2, PAX6, PITX2, PITX3, RAB18, RAB3GAP1, RAB3GAP2, RARB, RAX, RBP4, SALL2, SALL4, SHH, SIX3, SMCHD1, SMOC1, SOX2, STRA6, TBC1D20, VAX1, VSX2, YAP1, ZEB2 and ZIC2.
For more details please read the Ocular Malformation gene panel information sheet (PDF format)
ABCA4 gene sequencing
The ABCA4 gene encodes an adenosine triphosphate (ATP)-binding cassette transporter (ABCR) expressed specifically in the cones and rods of the retina. Variants in ABCA4 underlie a number of retinal / macular dystrophies: Stargardt disease, an autosomal recessive macular dystrophy often presenting within the first two decades of life, between 30 to 60% of incidences of autosomal recessive cone rod dystrophy and a small proportion of retinitis pigmentosa cases. This test provides sequencing of 100% of the coding regions and flanking intronic sequences of the ABCA4 gene as well as a number of deep intronic regions encompassing the previously reported pathogenic/likely pathogenic variants.
For more details please read the ABCA4 gene sequencing information sheet (PDF format)
Primordial Dwarfism and Microcephaly gene sequencing
Primordial dwarfism and microcephaly are genetically diverse disorders of brain and body growth. There are several biological processes that have been implicated in these conditions, such as DNA damage response, DNA replication and centrosome function. This test provides sequencing of coding regions and flanking intronic sequences for 60 genes associated with primordial dwarfism and/or microcephaly: ANKRD11, ASPM, ATR, ATRX, BLM, CASK, CDC45, CDC6, CDKN1C, CDK5RAP2, CDT1, CENPF, CENPJ, CEP135, CEP152, CEP63, CREBBP, DNA2, DNMT3A (PWWP domain only), DONSON, DPP6, DYRK1A, EP300, GMNN, IGF1, IGF1R, KIF11, KMT2A, KNL1, LARP7, LIG4, MCPH1, MRE11, NBN, NDE1, ORC1, ORC4, ORC6, PCNT, PLK4, PNKP, POC1A, POLE, RAD50, RBBP8, RNU4ATAC, SMARCAL1, SRCAP, STIL, TCF4, TOP3A, TRAIP, TUBGCP6, VPS13B, WDR4, WDR62 and XRCC4.
For more information please read the Microcephaly information sheet (PDF format)
Cornelia de Lange Syndrome (CdLS) gene sequencing
Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder with distinctive facial appearance, intellectual disability and growth failure as prominent features, displaying a wide spectrum of severity. Recent evidence shows that there is clinical and molecular overlap between atypical CdLS and other developmental disorders such as KBG syndrome and Wiedemann-Steiner syndrome. Somatic mosaicism has also emerged as a significant disease mechanism in CdLS. This test provides sequencing of 100% of the coding regions and flanking intronic sequences of nine genes (including somatic mosaic variants): NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, KMT2A, BRD4 and PUF60 as well as genomic regions containing the known pathogenic variants in AFF4 and NAA10 (p.Arg83Cys).
For more details please read the Cornelia de Lange Syndrome panel technical information sheet (PDF format)
Osteogenesis Imperfecta (OI) gene sequencing
Osteogenesis imperfecta (OI) is a brittle bone dysplasia, associated with bone fragility and deformity. This results in susceptibility to fractures and growth deficiency. OI can also be associated with dental abnormalities and hearing loss. The severity and associated phenotypes can vary considerably between patients. Variants in a number of genes have been associated with OI. This test provides sequencing of >95% of the coding regions and flanking intronic sequences of 19 genes associated with OI: BMP1, COL1A1, COL1A2, CREB3L1, CRTAP, FAM46A (TENT5A), FKBP10, IFITM5, KDELR2, P3H1, PLOD2, PLS3, PPIB, SERPINF1, SERPINH1, SP7, SPARC, TMEM38B and WNT1
For more details please read the Osteogenesis Imperfecta gene panel information sheet (PDF format)
Hereditary Ataxia and Hereditary Spastic Paraplegia gene sequencing
The hereditary ataxias are a group of disorders associated with an uncoordinated gait, a poor coordination of limbs and speech. Hereditary spastic paraplegia (HSP) is characterised by lower limb spasticity and weakness. Variants in a number of genes have been associated with adult-onset hereditary ataxia (HA) and HSP. This test provides sequencing of >95% of the coding regions and flanking intronic sequences of 70 genes associated with HA and HSP: AAAS, ABCB7, ABCD1, ADAR, AFG3L2, ALS2, ANO10, APTX, ATL1, ATM, ATP1A3, ATP7B, BSCL2, CACNA1A, CACNA1G, CAPN1, COQ8A, CYP27A1, CYP7B1, DDHD2, FA2H, FGF14, FTL, FXN, GBA2, GCH1, GRID2, HSPD1, IFI1H, ITPR1, KCNA1, KCNC3, KCND3, KIF1A, KIF5A, L1CAM, NIPA1, OPA3, PDYN, PLP1, PNPLA6, POLG, PRKCG, PRNP, PRRT2, REEP1, RNaseH2B, RTN2, SACS, SETX, SIL1, SLC1A3, SLC2A1, SPART, SPAST, SPG11, SPG21, SPG7, SPTBN2, STUB1, SYNE1, TGM6, TMEM240, TTBK2, TTPA, TWNK, UBAP1, VPS13D, WASHC5 and ZFYVE26
The criteria for testing are:
- Exclusion of metabolic, neoplastic, alcohol, and drug-related causes
- Normal/routine neurological bloods, and vitamin E testing
- Negative spinocerebellar ataxia repeat expansion panel, including FXTAS and FA testing
- MRI neuroimaging normal, or isolated cerebellar atrophy
- Family history of ataxia, or young age of onset (<50)
A pro forma for HSP testing is located on the Request Forms page.
For more details please read the Hereditary Ataxia and Hereditary Spastic Paraplegia gene panel information sheet (PDF format)
Bleeding and Platelet gene sequencing
The bleeding and platelet gene panel provides sequencing for genes involved in coagulation, fibrinolysis and platelet disorders for referrals from Haematology clinics. It targets genes involved in specific factor deficiencies and platelet genes involved in predispositions to bleeding and/or thrombosis. The panel includes three main subpanels: coagulation and fibrinolysis, platelet and thrombosis. Some smaller subpanels are also available where clinical indications suggest involvement of a specific gene or small number of genes, please contact the laboratory if required
For more details please read the Bleeding & Platelet technical information sheet (PDF format)
Combined Neurodegeneration, Hereditary Ataxia and Hereditary Spastic Paraplegia gene sequencing
For appropriate referrals, the neurodegeneration and hereditary ataxia/hereditary spastic paraplegia gene panels can be analysed in combination (see above sections for referral criteria).
For more details please read the Neurodegeneration, Hereditary Ataxia and Hereditary Spastic Paraplegia gene panel information sheet (PDF format).
Erythrocytosis gene sequencing
The Erythrocytosis gene panel is a custom probe set that includes green list genes from the Hereditary Erythrocytosis panel app panel R405 v1.19
The criteria for testing are Idiopathic erythrocytosis with:
- No acquired JAK2 variants
- Secondary causes excluded
- Young onset and/or family history
For more details please read the please see the Erythrocytosis gene sequencing technical information sheet (PDF format).
OTC gene sequencing
Ornithine transcarbamylase (OTC) deficiency is associated with hemizygous or heterozygous variants in the OTC gene, which is located on the X chromosome. This test provides sequencing of 100% of the coding regions and flanking intronic sequences of the OTC gene as well as a number of deep intronic regions encompassing previously reported pathogenic/likely pathogenic variants.
For more details please read the please see the OTC gene sequencing technical information sheet (PDF format).
CFTR gene sequencing
Cystic fibrosis (CF) and CFTR-related disease are autosomal recessive disorders associated with homozygous or compound heterozygous variants in the CFTR gene. This test provides full CFTR gene analysis for the detection of rare sequence variants in patients where a second variant has not been detected on the CF common variant screen, the detection rate of the common screen is low due to ethnicity or urgent cases where fetal echogenic bowel has been detected on antenatal scan. This test provides sequencing of 100% of the coding regions and flanking intronic sequences of the CFTR gene as well as a number of deep intronic regions encompassing previously reported pathogenic/likely pathogenic variants.
For more details please read the please see the CFTR gene sequencing technical information sheet (PDF format).
Iron Regulation gene sequencing
The Iron regulation gene panel is a custom probe set that includes green list genes from the Iron metabolism panel app panel R96 v1.2
The criteria for testing are;
- Juvenile Haemochromatosis (<30years) with severe iron overload in liver AND/OR heart. Raised serum ferritin >1000ug/L and transferrin saturation >90%
- Juvenile Haemochromatosis >30 years with unexplained severe haemochromatosis and HFE negative
- Ferroportin disease: raised serum ferritin with normal transferrin saturation and evidence of reticuloendothelial iron staining on liver biopsy or splenic iron overload on MRI and HFE mutations negative
- Haemochromatosis: raised serum ferritin and transferrin saturation C282Y negative
- Hereditary Hyperferritinemia cataract syndrome: High and constant levels of serum ferritin unresponsive to iron depletion and no signs of iron overload and no relevant clinical symptoms apart from visual impairment by cataract
- Biochemical evidence of unexplained iron overload and lack of homozygous/compound homozygous HFE mutations
- Iron Refractory Iron Deficiency Anaemia (IRIDA): Very low mean corpuscular volume (MCV) and low serum iron and low transferrin saturation, normal ferritin or ferritin levels in the lower limits of normal, no response to oral iron treatment
For more details please read the please see the Iron Regulation gene sequencing technical information sheet (PDF format).
Severe Developmental Disorders
Our laboratory offers an exome-based diagnostic service to patients presenting with a severe developmental disorder who have been seen by a consultant clinical geneticist and meet the following referral criteria: severe neurodevelopmental disorder and congenital anomalies, or abnormal growth parameters, or dysmorphic features, or unusual behavioural phenotype. Trio-based analysis of the DDG2P gene panel (https://www.ebi.ac.uk/gene2phenotype) is performed, which provides sequencing of >95% of the coding regions and flanking intronic sequences of DDG2P genes with a confidence category of moderate, strong, or definitive. According to the current literature, this test will detect an intragenic pathogenic variant in approximately 33% of cases with a severe developmental disorder (PMID: 29323667). For further information about this service and details of sensitivity and specificity of the test, please refer to Severe developmental disorders technical information (PDF format).
