Central Manchester & Manchester Childrens University Hospital


Cytogenetics - Services Provided

Prenatal Diagnosis Rapid Aneuploidy Screening Paediatric and Adult Investigations Rapid Aneuploidy FISH Molecular Cytogenetic Diagnosis Solid Tissue Investigations Cytogenetics Reports Download Request Card Useful Links Prenatal Diagnosis on pregnancies at risk of chromosome abnormality because of :- Down syndrome screen indication maternal age abnormal ultrasound scan family history of abnormality Samples:- amniotic fluid, obtained at 14-18 weeks gestation chorionic villi - for pregnancies at a high risk of cytogenetic abnormality (biopsies from 10 weeks gestation) Specimens:- 10-20ml of amniotic fluid in sterile universal. Greater than 12ml is required if both rapid aneuploidy screening and karyotyping are required. a minimum of 10-20mg chorionic villus aspirate in 10ml sterile transport medium in universal container -available from the laboratory (call 0161 276 6118) see contact details if you require further information NUMBERS OF CELLS EXAMINED The number of cells examined from each case varies according to the reason for referral. Usually a minimum of 10 cells is examined. In some cases this may be extended, for example if mosaicism is suspected For prenatal diagnosis more than one separate cell culture is usually examined Results are reported taking full account of scan findings and other relevant prenatal tests. It will sometimes be necessary to examine parental blood samples in order to interpret prenatal results fully Back to Top Rapid Aneuploidy Screening The Quantitative Fluorescent Polymerase Chain Reaction (QF-PCR) test identifies aneuploidy in uncultured amniotic fluid cells for markers on chromosomes 13, 18 & 21, providing information on copy number for specific regions of these chromosomes. Hence it can indicate that the fetus is likely to be affected with Trisomy 13 (Patau syndrome), Trisomy 18 (Edwards syndrome) or Trisomy 21 (Down syndrome). QF-PCR will be offered to all patients, provided the amniotic fluid sample fulfils the sample requirements (12ml or greater of amniotic fluid that is not blood stained or discoloured). Where ultrasound findings indicate a possible diagnosis of Turner Syndrome, rapid screening will be carried out using a Fluorescent In Situ Hybridisation (FISH) based test which also identifies the sex chromosomes. The test is a commercial product: it has FDA approval in the USA. The manufacturers recommend that it is not used as a stand alone test for making clinical decisions. Both the QF-PCR and the FISH tests are rapid since there is no requirement for cell culture. Limitations - Rapid Aneuploidy Screening Some samples will fail to give a result. Not all cytogenetic abnormalities will be detected. It is possible therefore that a patient given a normal QF-PCR/FISH result will have an abnormality reported on the standard chromosome analysis. There may be some false negative results, caused by maternal cell contamination. Some samples will not be suitable - in samples from early gestations there may be too few cells present. In some cases, parental blood samples will be required to help us interpret rare complex findings. We will request these by telephone when required. (10ml blood in EDTA tubes) Reporting of rapid aneuploidy results The report will indicate whether the fetus is likely to be affected/not affected with any of the aneuploidies listed above. Reporting times may vary. Abnormal QF-PCR results are confirmed by FISH prior to being reported adding 24hr to the reporting time. Rapid aneuploidy testing will not be available on some days during particular Bank Holiday periods. Samples received on the days that the test is not available will be processed for chromosome analysis as usual. We will issue a letter in advance of these occasions, giving details. Back to Top Paediatric and Adult Investigations on children and adults with mental handicap on infants with developmental delay and dysmorphic features for primary infertility/amenorrhea or abnormal sexual development (to exclude sex chromosome abnormalities) on individuals with a poor reproductive history (to screen for balanced chromosome rearrangements) on individuals suspected of having a chromosome breakage syndrome (Fanconi Anaemia, Bloom Syndrome, Nijmegen Breakage Syndrome, Ataxia Telangiectasia, Roberts Syndrome) for relatives of patients with a structural chromosome abnormality who may be at risk of having a handicapped child. sperm and egg donors Samples:- blood lymphocytes skin biopsy - after discussion with the department Specimens:- blood 5ml blood (adults) or 1ml blood (babies) in lithium heparin - store at 4°C overnight if necessary - samples should arrive within 24 hours of being taken skin(after discussion)10-20mg dermal biopsy in sterile saline or dry sterile container - may be stored at 4°C overnight if necessary Back to Top Rapid Aneuploidy FISH can be performed on newborns with suspected Down, Edwards, or Patau Syndromes and those with ambiguous genitalia. This test is carried out in addition to the standard cytogenetic analysis. Provisional results will typically be telephoned to the consultant on the next working day, provided samples arrive at the laboratory before 15:30. A provisional report may be faxed if a suitable fax number is provided. Back to Top Molecular Cytogenetic Diagnosis diagnosis of major gene deletions detection of cytogenetic microdeletion rapid aneuploidy testing in newborns Most common indications for molecular cytogenetics 22q deletion syndromes carrier status for Becker or Duchenne muscular dystrophies Wolf Hirschhorn (4p-) syndrome Cri du Chat (5p-) syndrome Miller Dieker syndrome WAGR NF2 Angelman/Prader Willi syndrome Williams syndrome Smith-Magenis syndrome Rubenstein Taybi syndrome The diagnostic potential of this test continues to expand (please ring the laboratory for current availability) Samples:-blood lymphocytes Specimens:- 5ml blood (adults) or 1ml blood (babies) in lithium heparin - store overnight at 4°C if necessary Samples should arrive within 24 hours of being taken Back to Top Solid Tissue Investigations Confirmation of prenatal diagnosis of chromosome abnormality. In cases with aneuploidy confirmation will be carried out by FISH. Ultrasound scan diagnosis of structural abnormality Phenotype suggestive of chromosome abnormality Confirmation or diagnosis of mosaic chromosome abnormality in patients known to the genetic counselling clinic Chromosome analysis will not be carried out routinely on samples which do not fulfill these criteria. Samples:- skin biopsy, cord, placental membrane Specimens Full depth skin biopsy (0.5cm3) Cord sample Placental membrane near cord insertion site Cord or cardiac blood in lithium heparin may accompany solid tissue samples Fetuses cannot be accepted by the laboratory under any circumstances. Samples of solid tumors should be sent to the Cytogenetics laboratory at the Christie Hospital. Back to Top Cytogenetics Reports Policy on telephone reporting - Following a telephone enquiry normal results may be given to a clinician, clinic sister or the referring clinician's secretary. Abnormal results from prenatal diagnosis may only be given to the referring consultant or their registrar For postnatal tests, results which confirm the clinical diagnosis may only be given to the clinician, clinic sister or clinician's secretary. Results in contradiction to a previous diagnosis or establishing a new diagnosis may only be given to the referring clinician. Telephone reports of a normal prenatal diagnosis do not include the gender of the fetus. Reporting Times The laboratory aims to report results on all:- urgent blood samples within 7 working days routine blood samples within 28 days rapid anauploidy tests within 2 working days prenatal diagnoses within 14 days. solid tissues within 28 days Non-urgent samples lacking adequate details of the referring clinician or hospital will not be reported until the laboratory is contacted by the referring centre and provided with appropriate confirmatory details. This strategy, which is necessary to preserve patient confidentiality may lead to increased reporting times. Back to Top Download Request Card Click here to download a request card Back to Top Links to some websites you might find useful Click here for links to some websites you might find useful Back to Top