Application to be an additional provider for existing test on the NHS Directory of Molecular Genetic Testing Additional Provider form

Transcription

1 Application to be an additional provider for existing test on the NHS Directory of Molecular Genetic Testing Additional Provider form Disease: Gene: Cystic Fibrosis (CF) (carrier testing in reproductive donors) CFTR Test Disease Population Triad Disease name and description (please provide any alternative names you wish listed) (A)-Testing Criteria Cystic Fibrosis carrier screening among reproductive tissue donors OMIM number for disease Gene name and description Cystic Fibrosis Transmembrane Conductance Regulator; CFTR (please provide any alternative names you wish listed) OMIM number for Gene Mutational spectrum for which you test 29 or 33 mutation kit Or 4-mutation (as for newborn screen), Technical Method (s) Validation Process Note please explain how this test has been validated for use in your laboratory How many reports have you produced for this test? NB please give the number of mutation positive/negative samples you have reported For how long have you been providing this service? Is there specialised local clinical/research expertise for this disease? Are you testing for other genes/diseases closely allied to this one? Please give details 29 or 33 CFTR mutation kit Or 4-mutation (as for newborn screen), (4-mut. kit detects only classic CF mutations, and counselling of donor is more straightforward. It may also be cheaper) Yes No Please provide details Cystic Fibrosis Other CFTR-related disorders - bronchiectasis, chronic pancreatitis 1

2 - CBAVD Your Activity How many tests do you (intend to) provide annually in your laboratory? 2

3 Target Population The essential clinical or family history features defining the target population must be described. (C)-Testing Criteria Reproductive tissue (egg or sperm) donors They are at population CF-mutation carrier risk, but owing to potential use for multiple recipients, are at higher than normal risk for giving rise to a CF child. (eg. A donor who is a CF carrier and is used successfully once each for 10 recipients, has a 1 in 9 chance of giving rise to a child with CF) Estimated prevalence of disease in the target population The normal population carrier frequency will apply, according to ethnic background. (ie. 1 in 24 for N.Europeans) A 29 or 33-mutation kit will detect 90% of carriers ie. 1 in 26 will be detected carriers; for the 86% detection from a 4-mutation test,1 in 28 will be detected carriers. Epidemiology Estimated prevalence of disease in the general UK population Please identify the information on which this is based Estimated gene frequency (Carrier frequency or allele frequency) Please identify the information on which this is based CF Incidence: approx. 1 in 2300 births in UK; - but differs greatly in different racial groups. 1 in 24 in UK Caucasian population are carriers Carrier frequency : % mutns detected racial-origin-dependent df508 4-mut.kit 29/33 mut.kit 1 in 24 in Caucasian English 75 % 81 % 90 % 1 in 60 in African-American 48 % 50 % 1 in 50 in UK Asian 28 % 28 % 29 % 1 in 23 in S.Europe 50 % 58 % 1 in 90 in non-specified Asian <30 % 1 in 280 in Japanese Asian 1 in 45 in Mexico <57 % 1 in 23 in Ashkenazi Jewish 43 % 97 % * *(W1282X = 37%) Test Characteristics Analytical sensitivity and specificity This should be based on your own laboratory data for the specific test being applied for or the analytical sensitivity and specificity of the method/technique to be used in the case of a test yet to be set up. Testing Strategy : 29 /33 mutation kit detects 90 % of N.European carriers 4-mutation test (F508del, G551D, G542X, 621+1G>T) detects 86% of UK carriers. Identified carriers would be refused as prospective donors (principally on account of potential use with multiple recipients). Alternatively, there is a valid argument here for testing the recipients, and giving the chance to proceed with a CF carrier 3

4 If a number of genes will be tested, please include your testing strategy and data on the expected proportions of positive results for each part of the process. It may be helpful to include a diagram to illustrate the testing strategy. donor for non-carriers if they wish. Test Sensitivity: This is dependent on racial origin (see Epidemiology section above). For UK Caucasians : 29/33 mutn kit will detect ~ 90 % of CF carriers 4 mutn. kit will detect heterozygous mutation in ~ 86 % of CF carriers Specificity : Caution is needed for interpretation of certain mutations eg. R117H and I148T mutations, if included in the 29/33 kit. Counselling of the donor for these and other mild mutations is not straightforward. The 4-mutation kit has is specific for true CF mutations, and consequent donor counselling is straightforward. 4

5 Referral Pathway Template TARGET POPULATION (Description) Prospective Reproductive tissue (egg or sperm) donors, at population CF carrier risk. WHAT TYPE AND LEVEL OF PROFESSIONAL OR REFERRER DO YOU ACCEPT SAMPLES FROM? Reproductive Medicine Specialist PLEASE PROVIDE DETAILS OF HOW REFERRALS WILL BE ASSESSED FOR APPROPRIATENESS? The only criteria for appropriateness is that these are potential egg or sperm donors HOW MANY TESTS DO YOU PERFORM ANNUALLY? 5

6 UKGTN Testing criteria for disease: Name of Disease(s): CF carrier testing in prospective egg or sperm donor (219700) Name of gene(s): Cystic Fibrosis Transmembrane Conductance Regulator; CFTR (602421) Patient name: Patient postcode: Date of birth: NHS number: Name of referrer: Title/Position: Lab ID: Referrals will only be accepted from one of the following: Referrer Reproductive Medicine Specialist Tick if this refers to you. Minimum criteria required for testing to be appropriate as stated in the Gene Dossier: Criteria Prospective egg or sperm donor Tick if this patient meets criteria If the sample does not fulfil these criteria and you still feel that testing should be performed please contact the laboratory to discuss testing of the sample. 6