title: A national perspective on prenatal testing for mitochondrial disease.
abstract: Mitochondrial diseases affect >1 in 7500 live births and may be due to mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Genetic counselling for families with mitochondrial diseases, especially those due to mtDNA mutations, provides unique and difficult challenges particularly in relation to disease transmission and prevention. We have experienced an increasing demand for prenatal diagnostic testing from families affected by mitochondrial disease since we first offered this service in 2007. We review the diagnostic records of the 62 prenatal samples (17 mtDNA and 45 nDNA) analysed since 2007, the reasons for testing, mutation investigated and the clinical outcome. Our findings indicate that prenatal testing for mitochondrial disease is reliable and informative for the nuclear and selected mtDNA mutations we have tested. Where available, the results of mtDNA heteroplasmy analyses from other family members are helpful in interpreting the prenatal mtDNA test result. This is particularly important when the mutation is rare or the mtDNA heteroplasmy is observed at intermediate levels. At least 11 cases of mitochondrial disease were prevented following prenatal testing, 3 of which were mtDNA disease. On the basis of our results, we believe that prenatal testing for mitochondrial disease is an important option for couples where appropriate genetic analyses and pre/post-test counselling can be provided.
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, The Medical School, Institute for Ageing and Health, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Nesbitt
authors.affiliation: NHS Specialised Services for Rare Mitochondrial Disorders of Adults and Children UK, Oxford, UK.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Alston
authors.affiliation: NHS Specialised Services for Rare Mitochondrial Disorders of Adults and Children UK, Oxford, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Blakely
authors.affiliation: 1] NHS Specialised Services for Rare Mitochondrial Disorders of Adults and Children UK, Oxford, UK [2] Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: Carl
authors.initials: C
authors.lastname: Fratter
authors.affiliation: NHS Specialised Services for Rare Mitochondrial Disorders of Adults and Children UK, Oxford, UK.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Feeney
authors.affiliation: 1] NHS Specialised Services for Rare Mitochondrial Disorders of Adults and Children UK, Oxford, UK [2] Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Poulton
authors.affiliation: 1] NHS Specialised Services for Rare Mitochondrial Disorders of Adults and Children UK, Oxford, UK [2] Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: Garry K
authors.initials: GK
authors.lastname: Brown
authors.affiliation: 1] Wellcome Trust Centre for Mitochondrial Research, The Medical School, Institute for Ageing and Health, Newcastle University, Newcastle-upon-Tyne, UK [2] NHS Specialised Services for Rare Mitochondrial Disorders of Adults and Children UK, Oxford, UK.
authors.forename: Doug M
authors.initials: DM
authors.lastname: Turnbull
authors.affiliation: 1] Wellcome Trust Centre for Mitochondrial Research, The Medical School, Institute for Ageing and Health, Newcastle University, Newcastle-upon-Tyne, UK [2] NHS Specialised Services for Rare Mitochondrial Disorders of Adults and Children UK, Oxford, UK.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.affiliation: 1] Wellcome Trust Centre for Mitochondrial Research, The Medical School, Institute for Ageing and Health, Newcastle University, Newcastle-upon-Tyne, UK [2] NHS Specialised Services for Rare Mitochondrial Disorders of Adults and Children UK, Oxford, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
mesh_terms: D015193:Chorionic Villi Sampling / Q000379:methods; D004272:DNA, Mitochondrial / Q000235:genetics*; D005817:Genetic Counseling; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008928:Mitochondria / Q000235:genetics; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D011296:Prenatal Diagnosis / Q000379:methods*
chemical_list: D004272:DNA, Mitochondrial