Molecular Genetics Laboratory Northern Genetics Service Northern Genetics Service Molecular Genetics Laboratory Information for Service Users 2017 Accredited Medical Laboratory Reference No: 2212 Laboratory address: Molecular Genetics Laboratory, Northern Genetics Service, Institute of Genetic Medicine (Bioscience East Wing), International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ. Head of Laboratory: Dr David Bourn (0191 241 8819, david.bourn@nuth.nhs.uk) If you require further information, please telephone the laboratory secretary (0191 241 8754) or service manager (0191 241 8775, Molecular.Genetics@nuth.nhs.uk) who will put you in contact with the appropriate member of the laboratory staff. Information is also available at https://www.newcastlelaboratories.com/ The laboratory is normally staffed between 8.30am and 5.00pm, Monday to Friday. Controlled document DO NOT photocopy. Inaccuracies or suggested improvements should be raised via EQMS Feedback. Page:0 of 16 Document ID: 3894 Document Title: Information for users 2017 Next Review Date: 30 Dec 2017 Document Owner: David Bourn Version: 2.9 Hard Copy Location: None Date Approved: 30 Dec 2016 16:52 Approved By: David Bourn Accessed by: David Bourn Accessed on: 30 Dec 2016 16:52 Before using a paper copy of this document check on EQMS to ensure the version is current and you have acknowledged any amendments.
Contents GenLYNC 3 Referral procedure 3 Sample transport 3 Hazardous samples 3 Consent for testing and storage of DNA 4 Quality assurance 4 UK Genetic Testing Network 4 Charging for services 4 Services available: 5 Alpha-1-antitrypsin deficiency 5 Angelman syndrome 5 Autoimmune polyendocrinopathy type 1 5 Bone marrow / stem cell transplant chimaerism monitoring 5 *Breast cancer: BRCA1 and BRCA2 6 Cartilage-hair hypoplasia 6 Chronic mucocutaneous candidaiasis 6 Cockayne syndrome Coffin Lowry syndrome 6 6 Connexin 26 related hearing loss 6 Connexin 32, X linked dominant Charcot Marie Tooth disease 7 Congenital adrenal hypoplasia 7 Cornelia de Lange syndrome 7 Cylindromatosis 7 Cystic fibrosis 7 DRPLA 8 Duchenne / Becker muscular dystrophy 8 Dystonia, primary torsion 8 Factor VII 8 Factor XI 8 *Familial adenomatous polyposis 9 Familial hypercholesterolaemia 9 Fragile X syndrome 9 Friedreich ataxia 9 Haemochromatosis 10 Haemolytic uremic syndrome 10 Haemophilia A and B 10 Hereditary spastic paraplegia 10 HMSN type1a / HNPP 11 *Lynch syndrome: MLH1, MSH2 and MSH6 11 Huntington disease 11 Identity testing 11 Limb girdle muscular dystrophy 12 MCAD deficiency 12 Microsatellite instability studies 12 *MYH associated polyposis (MAP) 12 Myotonic dystrophy type 1 13 Myotonic dystrophy type 2 13 Neuroferritinopathy 13 Prader willi syndrome 13 Rett syndrome 14 Simpson-Golabi-Behmel syndrome 14 Spinal muscular atrophy 14 Spinocerebellar ataxia types 1, 2, 3, 6, 7 and 17 14 Spinal and bulbar muscular atrophy 14 Molecular Genetics Laboratory User Manual 1
*von Hippel Lindau disease 15 von Willebrand disease 15 X-inactivation studies 15 Zygosity testing 15 Molecular Genetics Laboratory User Manual 2
GenLYNC: Genetics Laboratories - Yorkshire & Northern Collaborative Some of the tests for the disorders marked * in the contents list may be performed at the Yorkshire Regional Molecular Genetics Laboratory at St James Hospital, Leeds as part of a previous collaborative agreement between the two Regional Genetics Centres. Additional tests may also be carried out as part of collaborations with other laboratories, such as NewGene Ltd. However, all referrals should be made, as described below, to the Northern Genetics Service. Referral procedure 1. Blood samples should be provided in plastic EDTA tubes. 2. All sample tubes must be labelled with the following minimum information: Full name of the patient Date of birth of the patient 3. All samples should be accompanied by a DNA request card. If there is no card, the required information should be provided in a letter. DNA request cards are available, free of charge from: Hazel Forrest, Secretary to Molecular Diagnostic team. 0191 241 8754. A copy of the referral card can be found by following the links to Molecular Genetics at https://www.newcastlelaboratories.com/ 4. The information provided on the card must include: Full name of the patient Date of birth of the patient Sex of the patient NHS number of the patient Patient s postcode Tests required Name of referring clinician, address for issue of report and contact number Samples which do not conform to these criteria may be discarded. 5. Ensure that the name and date of birth on the card are exactly the same as those on the sample tube. Special care should be taken to ensure that forenames and surnames are clearly distinguished and gender is stated where there are potential ambiguities. Sample transport 1. Samples for molecular genetics should be delivered by post, courier, taxi or hospital delivery van to the reception desk of the Institute of Genetic Medicine. 2. Samples should be properly packaged by the referrer. Packaging should be strong and of good quality. In addition to the sample receptacle, here should be two further layers of packaging that should be closed and sealed to prevent any loss of contents. There should be sufficient cushioning to prevent breakage of the primary receptacle. The outer layer of packaging should be rigid. Please contact the laboratory (0191 241 8787 / 8775 / 8754) with any queries, and see Packing Instruction 650 as applied to UN3373 for further details. Alternatively, when samples are collected from patients attending clinics within the Institute, these should be delivered directly by the medical staff to Sample Reception. Samples collected out of normal laboratory working hours should be placed in the Sample Reception fridge, and this will be checked each morning by sample reception staff. 3. High risk samples should be clearly labelled in an appropriate manner (see below). Hazardous samples Samples known or suspected to be microbiological hazards must be identified as such by the use of appropriate hazard warning labels. Please contact the laboratory before referring samples from patients where a prion-related disorder is suspected. Molecular Genetics Laboratory User Manual 3
Consent for testing and storage of DNA Consent for DNA testing must be obtained from the patient by the referring clinician prior to referral of the sample. This is not the responsibility of the laboratory staff. Consent to store DNA after testing should also be obtained. If the patient does not wish their DNA to be retained in the laboratory, the appropriate opt out box on the referral form should be ticked. Quality assurance The Molecular Genetics Laboratory participates in the following external quality assurance schemes: UK NEQAS for Molecular Genetics (including blood spot testing for CF and MCADD) European Molecular Quality Network (EMQN) UK NEQAS for Histocompatibility and Immunogenetics (HFE genotyping and interpretation) UK NEQAS for Blood Coagulation (genetic analysis of bleeding disorders) UK NEQAS for Leucocyte Immunophenotyping (Post-SCT chimaerism monitoring, FLT3 and NPM1 testing) UK Genetic Testing Network (UKGTN) Molecular genetics tests that are not listed in this directory may be available at one of the other Regional Genetics Centres within the UK. Details of available tests and the provider laboratories are listed in the UKGTN Directory that can be found at www.ukgtn.org. Enquiries about tests that are available through the UKGTN and the provider laboratories can also be made to the Laboratory Service Manager, Molecular Genetics Laboratory, Northern Genetics Service (0191 241 8775, Molecular.Genetics@nuth.nhs.uk). The Northern Genetics Service regularly refers samples to the other Regional Genetics Centres but charges made for these tests may be the responsibility of the referring clinician. Where a clinical need exists and funding is available the Northern Genetics Service will be happy to discuss additions to the testing repertoire listed below. Please contact the Laboratory Service Manager (0191 241 8775) or Head of Laboratory (0191 241 8819) to discuss testing for specific disorders. Charging for services Please note that the list of services below includes some rare disorders not covered by the Northern Genetics Service contract, and therefore a charge may be applicable for referrals from within the Northern region. Any referrals from outside the Northern region and all non-nhs referrals will be charged. Please contact the Head of Laboratory (0191 241 8819) to discuss whether a charge is appropriate and for a test price list. Molecular Genetics Laboratory User Manual 4
Services available Alpha-1-antitrypsin deficiency Targeted mutation analysis for two commonly occurring mutations in the SERPINA1 gene: the Z allele (p.e366k) and the S allele (p.e288v). Confirmation of diagnosis in patients with clinical symptoms Carrier testing in relatives and partners of affected or carrier individuals Angelman syndrome Approximately 80% of cases of Angelman syndrome (AS) are due to lack of a maternally inherited copy of a critical region on chromosome 15 (15q11-q13). This may be due to deletion of the critical region or paternal hetero- or isodisomy. These are associated with a low recurrence risk. Imprinting mutations, parental chromosome 15 rearrangements, UBE3A mutations and other, currently undefined causes, account for the remaining 20% of cases and are associated with recurrence risks of up to 50%. Confirmation of diagnosis in children with clinical symptoms of AS Analysis of parental samples of positive cases to determine recurrence risk Prenatal diagnosis where there is a high recurrence risk Autoimmune polyendocrinopathy type 1 APS1 is a rare autosomal recessive condition caused by mutation of the AIRE-1 gene. 70% of mutant alleles in the British population carry a 13 base pair deletion in exon 8 (c.967_979del13) and a small number carry a point mutation in exon 6 p.(arg257*), [Pearce, S.H.S. et al., Am J Hum Genet 63: 1675-84 (1998)]. Confirmation of diagnosis in children with clinical symptoms of APS1 Carrier testing of relatives Prenatal diagnosis where there is a 1:4 risk 4 weeks 4 weeks Laboratory tests: Testing for the 13 base pair deletion in exon 8 and p.(arg257* in exon 6. Bone marrow / stem cell transplant chimerism monitoring Identification of donor alleles in post transplant blood and marrow samples following prior work-up. Pre-transplant work-up Post transplant monitoring Urgent referrals 5 days Laboratory tests: Analysis with 4 polymorphic markers to compare donor samples with those taken preand post transplant from the recipient. If these are not informative, a further 11 markers are available. Molecular Genetics Laboratory User Manual 5
Breast cancer Samples should be referred to the laboratory only after prior agreement with the Northern Genetics Service Clinical Genetics Dept. Contact Dr Paul Brennan (01642 282 673), Consultant Clinical Geneticist (Teesside) or Dr Alex Henderson (0191 241 8750), Consultant Clinical Geneticist (Newcastle) Full mutation search in high risk patients in BRCA1 Full mutation search in high risk patients in BRCA2 Presymptomatic /diagnostic testing for known familial mutation Cartilage-hair hypoplasia Full mutation search of the RMRP gene to confirm diagnosis in affected patients Carrier testing for relatives of patients with a known mutation Presymptomatic /diagnostic testing for known familial mutation Chronic mucocutaneous candidiasis Full mutation search of the STAT1 gene to confirm diagnosis in affected patients Presymptomatic /diagnostic testing for known familial mutation Cockayne syndrome Full mutation search of the ERCC8 (CSA) and ERCC6 (CSB) genes to confirm diagnosis in affected patients Carrier testing for relatives of patients with known familial mutation(s) Prenatal diagnosis Coffin Lowry syndrome Full mutation search of the RPS6KA3 (RSK2) gene to confirm diagnosis in affected patients Carrier testing for female relatives of CLS patients for known familial mutation Prenatal diagnosis for females who carry a CLS mutation Connexin 26related hearing loss Full mutation search of the connexin 26 gene in patients with clinical symptoms Carrier testing for relatives of patients with a known mutation Molecular Genetics Laboratory User Manual 6
Connexin 32 (X-linked dominant Charcot Marie Tooth disease, CMTX1) ( Full mutation search of the connexin 32 gene in patients with clinical symptoms Carrier testing for female relatives of patients with a known mutation Congenital adrenal hypoplasia Full mutation search of NROB1 in males with symptoms of AHC Carrier testing for female relatives of AHC patients with a known mutation Prenatal diagnosis for females who carry a NROB1 mutation Cornelia de Lange syndrome Full mutation search of NIPBL in patients with suspected Cornelia de Lange syndrome Mutation analysis in parents when a mutation has been identified in an affected child Cylindromatosis Full mutation search of the CYLD1 gene to confirm diagnosis in affected patients Presymptomatic /diagnostic testing for known familial mutation Cystic fibrosis Diagnostic testing in children with symptoms of CF. Neonatal screening subsequent to raised IRT Mutation searching in clinically diagnosed patients Prenatal diagnosis for carrier couples Mutation analysis in amniocytes where a fetus has been identified with an echogenic bowel on ultrasound scan. Carrier testing for adults within CF families for partners of carriers / affected individuals for males with azoospermia, including CBAVD for patients undergoing assisted conception procedures Primary mutation screen: 50 mutations Full mutation search Prenatal diagnosis Molecular Genetics Laboratory User Manual 7
Laboratory tests: 50 mutations in the CFTR gene are routinely tested (4 mutations initially for neonatal screening). Both legacy and standard HGVS nomenclature may be stated on reports issued by the laboratory. Specific testing for known rare mutations and full mutation analysis of CFTR where appropriate. Determination of intron 8 9T/7T/5T genotype in males with CBAVD, patients carrying a R117H mutation and patients with atypical presentation and one known mutation. Gene tracking using flanking markers and intragenic microsatellites- please contact the laboratory Dentatorubral-pallidoluysian atrophy (DRPLA) Diagnostic testing - detection of CAG repeat expansion Laboratory tests: Detection of CAG repeat expansion mutation in the atrophin 1 gene by PCR. Reports will indicate whether the expansion is within the normal range or the affected range. Actual repeat sizes will not be reported. Duchenne muscular dystrophy and Becker muscular dystrophy Diagnostic testing: Deletion and duplication analysis Carrier detection for females in DMD families Prenatal diagnosis Laboratory tests: Testing for exon deletions and duplications in the dystrophin gene. Gene tracking with flanking and intragenic microsatellite markers. Testing for known familial (non-deletion or duplication) mutations Dystonia, primary torsion A proportion of early-onset primary torsion dystonia (PTD) is due to deletion of the trinucleotide GAG in the TOR1A gene on chromosome 9q34. Age of onset and initial site of disease onset can be used as patient selection criteria [Bressman et al. Neurology (2000) 54: 1746-52]. Diagnostic testing for patients with PTD with onset before 26 years and with a limb as the initial site of onset 4 weeks Factor VII testing Full mutation search of the F7 gene in patients with clinical symptoms Carrier testing for relatives of patients with a known mutation Factor XI testing Full mutation search of the F11 gene in patients with clinical symptoms Carrier testing for relatives of patients with a known mutation Molecular Genetics Laboratory User Manual 8
Familial Adenomatous Polyposis Coli Full mutation search of the APC gene in clinically affected individuals Presymptomatic testing for members of FAP families where a causative mutation is known Gene tracking using flanking markers Familial Hypercholesterolaemia (FH) Full mutation search of the LDLR gene and targeted APOB and PCSK9 gene mutation analysis in clinically affected individuals (in collaboration with NewGene Ltd.) Presymptomatic and confirmatory testing for members of FH families where a causative mutation is known Please enquire FLT3 mutations in acute myeloid leukaemia A proportion of AML patients have mutations in the FLT3 gene that are prognostically important. FLT3 internal tandem duplication (ITD) and NPM1 gene 4bp duplication Fragile X syndrome Diagnostic testing for patients with clinical symptoms of fragile X syndrome, learning difficulties and delay in intellectual development. Carrier testing for members of fragile X syndrome families. Testing for premutations in patients with ataxia or premature ovarian failure Prenatal diagnosis. Stage 1 :Exclusion of CCG repeat expansion mutation in the FMR1 gene by PCR If exclusion is not possible, stage 2 testing is performed. Stage 2: Detection / exclusion of CCG repeat expansion mutation by TP-PCR Prenatal diagnosis In positive cases, reports will state whether the expansion is within the 'pre-mutation' or 'affected' range. The actual size of the expansion will not be reported for full mutations. Please contact the laboratory if methylation analysis is required. Friedreich ataxia Confirmation of diagnosis. Carrier testing for members of Friedreich ataxia families. Prenatal diagnosis Laboratory tests: Detection of GAA repeat expansion in intron 1 of the FXN gene by PCR. 98% of mutations are GAA repeat expansions. Actual repeat sizes will not be reported. Molecular Genetics Laboratory User Manual 9
Haemochromatosis Confirmation of diagnosis in patients with symptoms of haemochromatosis. Carrier testing for adult relatives of haemochromatosis patients. Laboratory tests: Detection of C282Y mutation in the HFE gene. Detection of H63D mutation in the HFE gene in C282Y heterozygotes. 4 weeks 4 weeks Haemolytic uremic syndrome Confirmation of diagnosis in clinically affected patients. Prenatal diagnosis following preparatory analysis in family. Mutation analysis in the CFH, CFI, CD46, C3 and CFB genes. Testing when causative mutation in family is known Prenatal diagnosis based on known familial mutation Haemophilia A and B Confirmation of diagnosis in patients diagnosed with haemophilia A or B. Carrier testing for female members of haemophilia A / B families. Prenatal diagnosis following preparatory analysis in family. Detection of intron 22 (50% of severe haemophilia A cases) and intron 1 inversions (<5% of severe haemophilia A cases) Predictive / confirmation test for known familial mutation Full mutation search of factor VIII / IX genes Gene tracking using flanking and intragenic markers 2-4 weeks 4 weeks Hereditary spastic paraplegia Mutation scanning by sequencing all coding exons of the SPAST (SPG4), ATL1 (SPG3A), REEP1 (SPG31) and SPG7 genes, plus MLPA for these genes. Full mutation search of the genes listed above in patients with clinical symptoms Family studies for relatives of patients with a known mutation Molecular Genetics Laboratory User Manual 10
Hereditary motor and sensory neuropathy type 1A (HMSN1) Hereditary neuropathy with liability to pressure palsies (HNPP) Also see Connexin 32. Testing is performed to confirm the presence of a duplication (HMSN1A) or deletion (HNPP) at chromosome 17p11.2-p12 involving the PMP22 gene. Confirmation of diagnosis. Prenatal diagnosis Lynch syndrome (hereditary non-polyposis colon cancer (HNPCC)) Samples should be referred to the laboratory only after prior agreement with the Northern Genetics Service Clinical Genetics Dept. Contact Dr Paul Brennan (01642 282 673), Consultant Clinical Geneticist (Teesside) or Dr Alex Henderson (0191 241 8750), Consultant Clinical Geneticist (Newcastle) Microsatellite instability studies (see below) Mutation search: MLH1, MSH2 and MSH6 Predictive / diagnostic test for known familial mutation Huntington disease Pre-symptomatic diagnosis to members of HD families who have undergone appropriate counselling. Diagnostic testing to individuals showing clinical features of HD. Referrals must be made through the Northern Region Clinical Genetics Service to whom results will be reported. Prenatal diagnosis to couples where a partner is affected or is a known mutation carrier. Prenatal exclusion testing where the 'at risk' parent has not taken a pre-symptomatic test. Detection of CAG repeat expansion mutation in the HTT gene If CCG polymorphic repeat analysis is necessary Prenatal testing: CAG repeat analysis or exclusion testing + Identity testing For paternity testing and other non-clinical identity tests please contact Northgene Ltd (Institute of Human Genetics, Central Parkway, Newcastle upon Tyne, NE1 3BZ). A fee is always charged and appointments should be made through the administrative office of the company (0191 241 8759). Testing with up to 15 highly polymorphic markers Molecular Genetics Laboratory User Manual 11
Limb Girdle Muscular Dystrophy (LGMD) This is a nationally funded service through the National Commissioning Group (NCG). For some genes, DNA testing will not be carried out unless protein analysis on a muscle biopsy specimen has been performed previously to determine the most likely causative gene. Referral enquiries should be made through Susan Robinson, NCG Limb-Girdle MD Referral Centre, Muscle Immunoanalysis Unit, Dental Hospital, Lower Ground Floor, Richardson Road, Newcastle upon Tyne, NE2 4AZ. Tel 0191 282 0841, email Susan.Robinson@nuth.nhs.uk A service is provided including the following genes associated with limb girdle muscular dystrophy LMNA, CAV3, CAPN3, DYSF, SGCA, SGCB, SGCD, SGCG, FKRP, MYOT,DES, CRYAB, ZASP, FHL1, VCP, ANO5, EMD, GNE, BAG3, DNAJB6 and TTN. Other services may be in development: please enquire. Confirmation of diagnosis. Carrier/pre-symptomatic testing when mutation(s) in family are known. Prenatal diagnosis when familial mutation(s) are known. Full mutation search Testing for known familial mutation Prenatal diagnosis per gene Medium chain acyl-coa dehydrogenase deficiency (MCAD) Confirmation of diagnosis. Carrier testing in relatives of affected patients. Prenatal diagnosis where there is a 1 in 4 risk. (5 days) + Laboratory tests: Detection of common mutation c.985a>g (K329E). This is present in 90% of defective MCAD genes in clinically affected individuals. + For neonatal screening referrals. Microsatellite instability studies Testing of tumour samples from patients with colorectal cancer to help direct subsequent mutation searching in Lynch syndrome causative genes. 2-4 weeks Laboratory tests: Tumour DNA is tested with a set of 5 mononucleotide repeat polymorphic markers. Immunohistochemistry for the common Lynch syndrome gene associated proteins is carried out in parallel: please enquire. Testing for BRAF codon 600 mutations is carried out where appropriate. MYH associated polyposis Confirmation of diagnosis in patients with suspected recessive polyposis colon cancer Carrier testing in relatives of affected patients. Laboratory tests: Detection of three known MYH mutations, p.tyr179cys, p.gly396asp and p.pro405leu. Molecular Genetics Laboratory User Manual 12
Myotonic dystrophy type 1 Diagnostic testing for patients with clinical symptoms of myotonic dystrophy Presymptomatic / carrier testing to members of DM families. Urgent referrals: Prenatal diagnosis Laboratory tests: Detection of CTG repeat expansion mutation in the DMPK gene. The actual size of any expansions will not be reported (with the possible exception of small expansions detected by standard PCR). Myotonic dystrophy type 2 Diagnostic testing for patients with clinical symptoms of myotonic dystrophy type 2 Presymptomatic / carrier testing to members of DM2 families. Urgent referrals: Prenatal diagnosis Laboratory tests: Detection of CCTG repeat expansion mutation in the ZNF9 gene. The actual size of any expansions will not be reported (with the possible exception of small expansions detected by standard PCR). Neuroferritinopathy This service is available to patients with a dominant family history of movement disorder or other relevant clinical features. Referrals should be made through the Clinical Genetics Dept. Diagnostic testing Presymptomatic testing where there is a confirmed family history. Laboratory tests: Detection of A insertion mutation at nucleotide 460 in the ferritin light chain gene (FTL c.460dupa). Rarer frameshifting mutations will also be detected by this test. Prader Willi syndrome Almost 100% of cases of Prader Willi syndrome are due to lack of a paternally inherited copy of a critical region on chromosome 15 (15q11-q13). This may be due to deletion of the critical region or maternal heteroor isodisomy. These are associated with a low recurrence risk. Imprinting mutations, parental chromosome 15 rearrangements, and other, currently undefined causes, account for a very small number of cases (<2%) and are associated with recurrence risks of up to 50%. Confirmation of diagnosis in children with clinical symptoms of PWS Analysis of parental samples of positive cases to determine recurrence risk from receipt of parental samples Prenatal diagnosis where there is a high recurrence risk Molecular Genetics Laboratory User Manual 13
Rett syndrome Full mutation analysis of MECP2 and CDKL5 in patients with clinical symptoms of Rett syndrome Prenatal diagnosis when familial mutation is known Simpson-Golabi-Behmel Syndrome Full mutation analysis of glypican 3 (GPC3) gene in children with clinical symptoms of SGB Carrier testing in female relatives when mutation is known. Prenatal diagnosis when familial mutation is known Spinal Muscular Atrophy Service offered and reporting times: Confirmation of diagnosis in individuals with clinical symptoms of SMA Carrier testing for individuals with a family history and their partners Prenatal diagnosis for known SMA deletion carriers Laboratory tests: Deletion screening of exons 7 and 8 of the SMN1 gene. Homozygous deletions and heterozygous deletions can be detected by this test. Spinocerebellar ataxia Types 1, 2, 3 (Machado-Joseph disease), 6, 7 and 17 Diagnostic testing Pre-symptomatic testing when an expansion mutation has been identified in an affected relative. Routine screen for all SCAs: Detection of CAG repeat expansions Specific single SCA locus: Detection of CAG repeat expansion Pre-symptomatic testing for familial cases Laboratory tests: Detection of CAG repeat expansion mutations in the following genes: ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7 and TBP. Reports will indicate whether the expansion is within the normal range or the affected range. Other than for expansions, actual repeat sizes will not normally be reported. Spinal and bulbar muscular atrophy (Kennedy's disease) Diagnostic testing - detection of CAG repeat expansion Carrier testing in female relatives Laboratory tests: Detection of CAG repeat expansion mutation in the X-linked androgen receptor gene. Reports will indicate whether the expansion is within the normal range or the affected range. Other than for expansions, actual repeat sizes will not normally be reported. Molecular Genetics Laboratory User Manual 14
von Hippel-Lindau disease Full mutation search of the VHL gene Predictive / diagnostic testing where familial mutation is known. von Willebrand disease Sequencing of exons 17-20 and 24-27 or exon 28 depending on type Predictive / diagnostic testing where familial mutation is known. X-inactivation studies This service is available when X skewed inactivation is a likely mechanism for manifestation of X linked recessive disorders in females. Testing methylation status at the androgen receptor locus enquire Zygosity testing This service is available when there is a clinical need to confirm the zygosity of twins. A charge will be made for non-clinical cases. Testing with up to 15 polymorphic markers Identical genotypes in twins gives >98.5% probability of monozygosity. This rises to >99% in most cases if parental samples are tested. Molecular Genetics Laboratory User Manual 15